Cancer Research and Treatment

Original Articles

Clinical Outcomes and Histologic Subtype-Specific Patterns in Oligometastatic Soft Tissue Sarcoma of the Extremities and Trunk Wall: Implications for Curative Local Ablative Therapy: Eunkyu Yang, Han-Soo Kim, Jay Hoon Park, Yongsung Kim, Shinn Kim, Miso Kim, Jeonghwan Youk, Hak Jae Kim, Hyun-Cheol Kang, Ilkyu Han; Received September 9, 2025 Accepted October 29, 2025 Published online October 30, 2025; DOI: https://doi.org/10.4143/crt.2025.983 [Accepted]

Abstract PDF: Purpose
Oligometastatic soft tissue sarcoma (STS) may offer the possibility of cure compared with polymetastatic disease, with progression patterns and treatment responses varying across histologic subtypes. This study investigated the clinical characteristics, oncologic outcomes, and histologic subtype-specific features of oligometastatic STS.
Materials and Methods
We reviewed records of 1,243 patients with extremity/trunk STS who underwent curative surgery between 2000 and 2023. Oligometastatic recurrence occurred in 170 (13.6%), 149 of whom received local ablative therapy (LAT). Disease-specific survival (DSS) and progression-free survival (PFS) were analyzed, along with prognostic factors and subtype-specific characteristics.
Results
The median follow-up was 52.5 months. Surgery alone was the most common LAT (71.2%), followed by surgery with radiotherapy, radiotherapy alone and radiofrequency ablation. The median DSS was 50.0 months (95% confidence interval [CI], 31.5-68.5), with a 5-year DSS rate of 45.2%. The median PFS was 12.0 months (95% CI, 7.6-16.4), with a 5-year PFS of 28.1%. On multivariate analysis, LAT was independently associated with longer DSS (hazard ratio [HR], 9.629; p<0.001). Smaller oligometastatic lesion size and adequate local control of the primary tumor were also independently associated with longer DSS. Metastasis-free interval > 6 months independently predicted longer PFS. Histologic subtypes demonstrated distinct clinical behaviors; for example, myxofibrosarcoma had a lower metastatic rate but poorer DSS, whereas synovial sarcoma showed relatively favorable long-term survival.
Conclusion
Oligometastatic STS represents an intermediate disease state in which LAT can provide meaningful survival benefit. Subtype-specific differences in metastatic behavior and survival outcomes would support individualized, multimodal, and potentially curative treatment strategies.

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Proteomic Analysis Identifies Association of Periostin, a Matricellular Protein, with High Tumor Stroma and Immune Exclusion in Triple-Negative Breast Cancer: Yeonjin Jeon, GunHee Lee, Byung-Kwan Jeong, Yoon Young Kim, JiSun Kim, Jae Ho Jeong, Kyunggon Kim, Hee Jin Lee; Received February 6, 2025 Accepted July 25, 2025 Published online July 28, 2025; DOI: https://doi.org/10.4143/crt.2025.145 [Accepted]

Abstract PDF: Purpose
Immune excluded/desert tumors show reduced responsiveness to immunotherapy compared to inflamed tumors. The tumor stroma contributes to immune evasion. This study aimed to identify proteins overexpressed in tumors with high tumor stroma among immune excluded triple-negative breast cancer (TNBC) to better understand the mechanisms of immune exclusion.
Materials and Methods
Proteomic analysis was conducted on formalin-fixed, paraffin-embedded samples from 403 cases of TNBC. We compared protein expression between stroma high vs. stroma low within the immune excluded subtype. We investigated the correlations between the identified protein expression and other clinicopathologic features. Immunohistochemical (IHC) staining and single-cell analysis were conducted, along with survival analysis.
Results
Among the 247 eligible cases, 81 (32.8%) were classified as immune excluded and 166 (67.2%) as inflamed. Within the excluded subtype, periostin was the only extracellular matrix-related protein significantly overexpressed in stroma high cases. Periostin expression demonstrated a positive correlation with the amount of stroma (r = 0.51, p<0.001) and a negative correlation with tumor-infiltrating lymphocytes (TILs) (r = −0.30, p<0.001). Periostin expression in the tumor stroma was confirmed by IHC. Single-cell analysis demonstrated that periostin originated from cancer-associated fibroblasts (CAFs). High periostin levels correlated with poorer recurrence-free survival (hazard ratio 1.422, p=0.005).
Conclusion
Periostin is overexpressed in stroma high, immune excluded TNBC and is derived from CAFs. Its expression is associated with reduced TILs and poor prognosis. The development of targeted agents against periostin-positive CAFs may help overcome immune evasion and improve the effectiveness of immunotherapy in TNBC.

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Microbial Dynamics Across Molecular Subtypes and Prognostic Significance of Lactobacillus in Gastric Cancer: Soo Kyung Nam, Juhyeong Park, Sujin Oh, Yoonjin Kwak, Cheol Min Shin, Kyoung Un Park, Nak-Jung Kwon, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Han-Kwang Yang, Hye Seung Lee; Received April 25, 2025 Accepted July 16, 2025 Published online July 17, 2025; DOI: https://doi.org/10.4143/crt.2025.449 [Accepted]

Abstract PDF: Purpose
Recent studies have revealed a diverse gastric microbiota beyond Helicobacter pylori, suggesting a role in gastric cancer (GC). We aimed to investigate the composition and characteristics of the microbiota in GC and non-cancerous gastric mucosa (NC), with a particular focus on their relationship to molecular subtypes.
Materials and Methods
We conducted 16S rRNA sequencing and whole transcriptomic analysis on fresh-frozen GC and NC tissue samples from 192 GC patients, as well as saliva samples from 12 GC patients and 18 healthy individuals. Microsatellite instability (MSI), Epstein-Barr virus (EBV) in situ hybridization, and immunohistochemistry for p53 and E-cadherin were used to define molecular subtypes.
Results
GC tissues exhibited significantly higher diversity compared to matched NC tissues, with microbial profiles marked by decreased Helicobacter and increased Streptococcus, Prevotella, and Lactobacillus. Saliva samples predominantly contained oral bacteria and exhibited distinct microbial profiles from gastric tissues. In GC tissue, Helicobacter abundance was negatively correlated with key immune checkpoint genes (CTLA-4, PDCD1, CD274, and LAG3), whereas Prevotella, Streptococcus, and Fusobacterium were positively correlated. MSI-high and EBV-positive subtypes showed lower levels of Helicobacter but higher levels of Lactobacillus, Prevotella, and Streptococcus compared to the epithelial-mesenchymal transition (EMT)-like subtype. Notably, within MSI-H GC, a subgroup characterized by Lactobacillus-enriched and otherwise microbiota-depleted profiles was significantly associated with poorer overall and disease-free survival.
Conclusion
These findings underscore distinct microbial patterns across GC molecular subtypes, suggesting potential biomarkers for GC diagnosis and treatment.

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Breast cancer

Impacts of Subtype on Clinical Feature and Outcome of Male Breast Cancer: Multicenter Study in Korea (KCSG BR16-09): Jieun Lee, Keun Seok Lee, Sung Hoon Sim, Heejung Chae, Joohyuk Sohn, Gun Min Kim, Kyung-Hee Lee, Su Hwan Kang, Kyung Hae Jung, Jae-ho Jeong, Jae Ho Byun, Su-Jin Koh, Kyoung Eun Lee, Seungtaek Lim, Hee Jun Kim, Hye Sung Won, Hyung Soon Park, Guk Jin Lee, Soojung Hong, Sun Kyung Baek, Soon Il Lee, Moon Young Choi, In Sook Woo; Cancer Res Treat. 2023;55(1):123-135. Published online March 24, 2022; DOI: https://doi.org/10.4143/crt.2021.1561

Abstract PDF Supplementary Material PubReader ePub

Purpose
The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea.
Materials and Methods
We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016.
Results
The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003).
Conclusion
Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.

Citations

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HER2 expression and pathway status in male breast cancer patients: results of an integrated analysis among 6,150 patients
Boqiang Lyu, Shidi Zhao, Hui Wang, Shouping Gong, Biyuan Wang
Scientific Reports.2025;[Epub] CrossRef
Male breast cancer - a single center experience
Igor Djurisic, Milan Zegarac, Milan Kocic, Vladimir Jokic, Nikola Vucic, Ognjen Petrovic, Nada Santrac, Jovana Koncar, Andjela Ivezic, Srdjan Nikolic
Srpski arhiv za celokupno lekarstvo.2025; 153(1-2): 53. CrossRef
Clinicopathologic Features and Prognoses of Male Patients With Breast Cancer
Meiling Huang, Jingjing Xiao, Changjiao Yan, Rui Ling, Ting Wang
American Journal of Men's Health.2024;[Epub] CrossRef

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Lung and Thoracic cancer

The Feasibility of Using Biomarkers Derived from Circulating Tumor DNA Sequencing as Predictive Classifiers in Patients with Small-Cell Lung Cancer: Yu Feng, Yutao Liu, Mingming Yuan, Guilan Dong, Hongxia Zhang, Tongmei Zhang, Lianpeng Chang, Xuefeng Xia, Lifeng Li, Haohua Zhu, Puyuan Xing, Hongyu Wang, Yuankai Shi, Zhijie Wang, Xingsheng Hu; Cancer Res Treat. 2022;54(3):753-766. Published online October 5, 2021; DOI: https://doi.org/10.4143/crt.2021.905

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Purpose
To investigate the feasibility of biomarkers based on dynamic circulating tumor DNA (ctDNA) to classify small cell lung cancer (SCLC) into different subtypes.
Materials and Methods
Tumor and longitudinal plasma ctDNA samples were analyzed by next-generation sequencing of 1,021 genes. PyClone was used to infer the molecular tumor burden index (mTBI). Pre-treatment tumor tissues [T1] and serial plasma samples were collected (pre-treatment [B1], after two [B2], six [B3] cycles of chemotherapy and at progression [B4]).
Results
Overall concordance between T1 and B1 sequencing (n=30) was 66.5%, and 89.5% in the gene of RB1. A classification method was designed according to the changes of RB1 mutation, named as subtype Ⅰ (both positive at B1 and B2), subtype Ⅱ (positive at B1 but negative at B2), and subtype Ⅲ (both negative at B1 and B2). The median progressive-free survival for subtype Ⅰ patients (4.5 months [95%CI: 2.6-5.8]) was inferior to subtype Ⅱ (not reached, p<0.0001) and subtype Ⅲ (10.8 months [95%CI: 6.0-14.4], p=0.002). The median overall survival for subtype Ⅰ patients (16.3 months [95%CI: 5.3-22.9]) was inferior to subtype Ⅱ (not reached, p=0.01) and subtype Ⅲ (not reached, p=0.02). Patients with a mTBI dropped to zero at B2 had longer median overall survival (not reached vs. 19.5 months, p=0.01). The changes of mTBI from B4 to B1 were sensitive to predict new metastases, with a sensitivity of 100% and a specificity of 85.7%.
Conclusion
Monitoring ctDNA based RB1 mutation and mTBI provided a feasible tool to predict the prognosis of SCLC.

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Cell-free and extrachromosomal DNA profiling of small cell lung cancer
Roya Behrouzi, Alexandra Clipson, Kathryn L. Simpson, Fiona Blackhall, Dominic G. Rothwell, Caroline Dive, Florent Mouliere
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Sara Santamaria, Barbara Cardinali, Matteo Rovere, Silvia Marconi, Simone Nardin, Gianluca Sacco, Lucrezia Barcellini, Lucia Del Mastro, Carlo Genova, Simona Coco
Critical Reviews in Clinical Laboratory Sciences.2025; 62(6): 404. CrossRef
Liquid biopsy in diagnosis and monitoring of treatment efficacy in patients with small cell lung cancer
Natalia Galant, Anna Grenda, Paweł Krawczyk, Mateusz Pięt, Janusz Milanowski
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Intercalated Avelumab plus platinum-based chemotherapy in patients with Extensive-Stage Small-Cell Lung cancer (PAVE): Final outcome, immunophenotypic and biomarker analysis of a multi-center phase II Hellenic Cooperative Oncology Group study
Helena Linardou, Kyriaki Papadopoulou, Nikolaos Korfiatis, Anna Goussia, Epaminondas Samantas, Gerasimos Aravantinos, Athina Christopoulou, Nikolaos Spathas, Elena Fountzilas, Amanda Psyrri, Georgia-Angeliki Koliou, Soultana Meditskou, Epaminondas Kosmas,
European Journal of Cancer.2025; 228: 115660. CrossRef
State of the art in treatment of small cell lung cancer
Roya Behrouzi, Fiona Blackhall
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Circulating tumor DNA as liquid biopsy in lung cancer: Biological characteristics and clinical integration
Changshu Li, Jun Shao, Peiyi Li, Jiaming Feng, Jingwei Li, Chengdi Wang
Cancer Letters.2023; 577: 216365. CrossRef
Prognostic and predictive impact of molecular tumor burden index in non‐small cell lung cancer patients
Fan Yang, Min Tang, Liang Cui, Jing Bai, Jiangyong Yu, Jiayi Gao, Xin Nie, Xu Li, Xuefeng Xia, Xin Yi, Ping Zhang, Lin Li
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Ugo Testa, Elvira Pelosi, Germana Castelli
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Impact of Angiotensin Receptor Blockers, Beta Blockers, Calcium Channel Blockers and Thiazide Diuretics on Survival of Ovarian Cancer Patients: Min Ae Cho, Soo Young Jeong, Insuk Sohn, Myeong-Seon Kim, Jun Hyeok Kang, E Sun Paik, Yoo-Young Lee, Chel Hun Choi; Cancer Res Treat. 2020;52(2):645-654. Published online January 16, 2020; DOI: https://doi.org/10.4143/crt.2019.509

Abstract PDF Supplementary Material PubReader ePub

Purpose
We investigated the impact of four types of antihypertensive medications, angiotensin receptor blockers (ARBs), beta blockers (BBs; both selective and non-selective), calcium channel blockers (CCBs), and thiazide diuretics (TDs) on survival outcomes in epithelial ovarian cancer (EOC).
Materials and Methods
A single-institutional retrospective chart review of 878 patients with EOC was performed. Survival was compared according to use of the four antihypertensive medications during primary treatment. Propensity score matching (ratio 1:3) was performed to control possible associated covariates, such as age, International Federation of Gynecology and Obstetrics stage, residual status after primary debulking surgery, and co-morbidity.
Results
Among 878 patients, 56 patients (6.4%) were ARB users, 62 (7.1%) were BB users, 107 (12.2%) were CCBs users and 32 (3.6%) used TDs. Median progression-free survival (PFS) for ARB, BB, and CCB users was 37.8, 27.2, and 23.6 months compared with 33.6 months for non-users. ARB was associated with 35% decreased risk of disease progression (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.42 to 0.99; p=0.046) in multivariate analysis. After propensity score matching, median PFS for ARB users was 37.8 months and ARB use remained to be associated with lower recurrence rate in univariate (p=0.035) and multivariate analysis (HR, 0.60; 95% CI, 0.39 to 0.93; p=0.022).
Conclusion
In this study, ARBs use during primary treatment is associated with lower recurrence in EOC patients. However, CCBs, BBs, and TDs did not show beneficial impact.

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Pian Wang, Xinmiao Zhang, Jinhai Shen
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Katarzyna Regulska, Paulina Gieremek, Marcin Michalak, Tomasz Kolenda, Marlena Janiczek-Polewska, Joanna Kozłowska-Masłoń, Zefiryn Cybulski, Beata J. Stanisz
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Genetically proxied therapeutic effect of antihypertensive drug use, breast cancer, and ovarian cancer’s risk: a drug-target Mendelian randomization study
Chunxiao Dang, Ruohan Wang, Yunzhen Shi, Pengfei Liu, Xiaofeng Wang, Jinxing Liu, Xiao Yu, Dongxu Jin, Qing Ma
BMC Cancer.2025;[Epub] CrossRef
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Xuye Wang, Xiangyang Xu, Wan Yin Tew, Liyun Ouyang, Xiaoning Yang, Hui Wei Loh, Wen Xu, Wei Xu, Mun Fei Yam
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Evaluation of antihypertensive medications use and survival in patients with ovarian cancer: a population-based retrospective cohort study
Rūta Everatt, Irena Kuzmickienė, Birutė Brasiūnienė, Ieva Vincerževskienė, Birutė Intaitė, Saulius Cicėnas, Ingrida Lisauskienė
BMC Women's Health.2024;[Epub] CrossRef
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Ruixing Zhang, Hongtao Yin, Mengdi Yang, Jinjin Liu, Donghu Zhen, Zheng Zhang
Journal of Hypertension.2024; 42(11): 1862. CrossRef
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Yao Xiao, Xinlong Chen, Wancheng Li, Xin Li, Wence Zhou
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Yuanyuan Fan, Nazeer Hussain Khan, Muhammad Farhan Ali Khan, MD Faysal Ahammad, Tayyaba Zulfiqar, Razia Virk, Enshe Jiang
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Zhao-Yan Wen, Song Gao, Ting-Ting Gong, Yu-Ting Jiang, Jia-Yu Zhang, Yu-Hong Zhao, Qi-Jun Wu
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Body Cavity–Based Lymphoma in a Country with Low Human Immunodeficiency Virus Prevalence: A Series of 17 Cases from the Consortium for Improving Survival of Lymphoma: Junghoon Shin, Young Hyeh Ko, Sung Yong Oh, Dok Hyun Yoon, Jeong-Ok Lee, Jin Seok Kim, Yong Park, Ho Jin Shin, Seok Jin Kim, Jong Ho Won, Sung-Soo Yoon, Won Seog Kim, Youngil Koh, On behalf of the Consortium for Improving Survival of Lymphoma investigators; Cancer Res Treat. 2019;51(4):1302-1312. Published online February 14, 2019; DOI: https://doi.org/10.4143/crt.2018.555

Abstract PDF PubReader ePub

Purpose
Primary effusion lymphoma (PEL) is a type of body cavity–based lymphoma (BCBL). Most patients with PEL are severely immunocompromised and seropositive for human immunodeficiency virus (HIV). We investigated the distinctive clinicopathologic characteristics of BCBL in a country with low HIV burden.
Materials and Methods
We retrospectively collected data on the clinicopathologic characteristics, treatments, and outcomes of 17 consecutive patients with BCBL at nine institutions in Korea.
Results
Latency-associated nuclear antigen 1 (LANA1) immunostaining indicated that six patients had PEL, six patients had human herpesvirus 8 (HHV8)-unrelated BCBL, and five patients had HHV8-unknown BCBL. The patients with PEL exhibited no evidence of immunodeficiency except for one who was HIV positive. One (20%) and four (80%) patients with PEL and six (100%) and zero (0%) patients with HHV8-unrelated BCBL were positive for CD20 and CD30 expression, respectively. The two patients with PEL (one HIV-positive and one HIV-negative patient) with the lowest proliferation activity as assessed by the Ki-67 labeling index survived for > 1 and > 4 years without chemotherapy, respectively, in contrast to the PEL cases in the literature, which mostly showed a high proliferation index and poor survival.
Conclusion
PEL mostly occurred in ostensibly immunocompetent individuals and had a favorable outcome in Korea. A watchful waiting approach may be applicable for managing HIV-seronegative patients with PEL with a low Ki-67 labeling index. A possible trend was detected among LANA1, CD20, and CD30 expression in BCBL.

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Kaposi sarcoma-associated herpesvirus cooperates with Epstein-Barr virus to co-transform a small set of human B cells oncogenically
Mitchell Hayes, Wei Wang, Isabela Fraga de Andrade, Paul F. Lambert, Bill Sugden, Paul M Lieberman
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Space-associated lymphomas: review of a heterogeneous group of old and new entities
Judith A Ferry
Diagnostic Histopathology.2024; 30(8): 430. CrossRef
A Comprehensive Clinicopathologic and Molecular Study of 19 Primary Effusion Lymphomas in HIV-infected Patients
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Zein Kattih, Akhilesh Mahajan, Morana Vojnic, Jordan Steinberg, Alyssa Yurovitsky, Jin Ah Kim, Amory Novoselac
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Human herpesvirus‐8–positive primary effusion lymphoma in HIV‐negative patients: Single institution case series with a multidisciplinary characterization
Giovanni Rossi, Ilaria Cozzi, Irene Della Starza, Lucia Anna De Novi, Maria Stefania De Propris, Aurelia Gaeta, Luigi Petrucci, Alessandro Pulsoni, Federica Pulvirenti, Valeria Ascoli
Cancer Cytopathology.2021; 129(1): 62. CrossRef
Primary effusion lymphoma in human immune deficiency (HIV)‐negative non‐organ transplant immunocompetent patients
Lisi Yuan, James R. Cook, Tarik M. Elsheikh
Diagnostic Cytopathology.2020; 48(4): 380. CrossRef
Clinicopathologic characteristics and survival of patients with primary effusion lymphoma
Cristian Aguilar, Caddie Laberiano, Brady Beltran, Cecilia Diaz, Alvaro Taype-Rondan, Jorge J. Castillo
Leukemia & Lymphoma.2020; 61(9): 2093. CrossRef

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A Nomogram for Predicting the Oncotype DX Recurrence Score in Women with T1-3N0-1miM0 Hormone Receptor‒Positive, Human Epidermal Growth Factor 2 (HER2)‒Negative Breast Cancer: Sae Byul Lee, Junetae Kim, Guiyun Sohn, Jisun Kim, Il Yong Chung, Hee Jeong Kim, Beom Seok Ko, Byung Ho Son, Sei-Hyun Ahn, Jong Won Lee, Kyung Hae Jung; Cancer Res Treat. 2019;51(3):1073-1085. Published online November 1, 2018; DOI: https://doi.org/10.4143/crt.2018.357

Abstract PDF Supplementary Material PubReader ePub

Purpose
This preliminary study was conducted to evaluate the association between Oncotype DX (ODX) recurrence score and traditional prognostic factors. We also developed a nomogram to predict subgroups with low ODX recurrence scores (less than 25) and to avoid additional chemotherapy treatments for those patients.
Materials and Methods
Clinicopathological and immunohistochemical variables were retrospectively retrieved and analyzed from a series of 485 T1-3N0-1miM0 hormone receptor-positive, human epidermal growth factor 2‒negative breast cancer patients with available ODX test results at Asan Medical Center from 2010 to 2016. One hundred twenty-seven patients (26%) had positive axillary lymph node micrometastases, and 408 (84%) had ODX recurrence scores of ≤25. Logistic regression was performed to build a nomogram for predicting a low-risk subgroup of the ODX assay.
Results
Multivariate analysis revealed that estrogen receptor (ER) score, progesterone receptor (PR) score, histologic grade, lymphovascular invasion (LVI), and Ki-67 had a statistically significant association with the low-risk subgroup. With these variables, we developed a nomogram to predict the low-risk subgroup with ODX recurrence scores of ≤25. The area under the receiver operating characteristic curve was 0.90 (95% confidence interval [CI], 0.85 to 0.96). When applied to the validation group the nomogram was accurate with an area under the curve = 0.88 (95% CI, 0.83 to 0.95).
Conclusion
The low ODX recurrence score subgroup can be predicted by a nomogram incorporating five traditional prognostic factors: ER, PR, histologic grade, LVI, and Ki-67. Our nomogram, which predicts a low-risk ODX recurrence score, will be a useful tool to help select patients who may or may not need additional ODX testing.

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Human Papillomavirus Genotype-Specific Persistence and Potential Risk Factors among Korean Women: Results from a 2-Year Follow-up Study: Cecile Ingabire, Min Kyung Lim, Young-Joo Won, Jin-Kyoung Oh; Cancer Res Treat. 2018;50(3):813-822. Published online August 17, 2017; DOI: https://doi.org/10.4143/crt.2017.340

Abstract PDF Supplementary Material PubReader ePub

Purpose
High-risk human papillomavirus (HPV) infection progression should be considered a critical factor for preventing cervical cancer, although most infections are transient and rarely persist. This study aimed to examine the specific types of HPV infections, their change patterns, and the potential risk factors among Korean women.
Materials and Methods
We included 4,588 women who visited hospitals in Busan and Suwon for cervical cancer screening, and 1,224 of thesewomen attended a 2-yearfollow-up. Infection statuswas evaluated using HPV DNA testing (Hybrid Capture 2) and genotyping testing (Linear Array). Data regarding the potential risk factors for HPV infection were collected by trained nurses using structured questionnaires.
Results
Among the 1,224 women (mean age, 47 years), 105 women (8.6%) were HPV-positive at baseline. HPV infections had been cleared among 92 women (87.6%) within 2 years. Only 13 infections (12.4%) were remained, and the 10 cases of them are high-risk HPV types including genotype 33, 45, 16, 35, and 52. Among women who were negative at baseline, the HPV incidence was 4.8%. The HPV incidence was marginally associated with having multiple sexual partners (odds ratio, 2.0; 95% confidence interval, 1.0 to 3.9), although it was not significantly associated with HPV persistence.
Conclusion
Most HPV infections (88%) among Korean women were cleared within 2 years, with only a small number of persistent infections. The persistent HPV genotypes were different in our study, compared to those from previous studies. Having multiple sexual partners was associated with acquiring a HPV infection, but not with persistence.

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High-Risk HPV Persistence and Clearance Patterns Among Women in Ethiopia: A Longitudinal Study
Brhanu Teka, Adamu Addissie, Adane Mihret, Muluken Gizaw, Welelta Shiferaw, Zewditu Chanyalew, Andreas Kaufmann, Eva Kantelhardt, Tamrat Abebe
International Journal of Women's Health.2025; Volume 17: 3799. CrossRef
Investigation of Human Papillomavirus (HPV) Frequency and Genotype Analysis in Cervical Samples
Yeliz Çetinkol, Selahattin Ünlü, Melahat Gürbüz, Cengiz Demir
Journal of Biotechnology and Strategic Health Research.2024; 8(1): 50. CrossRef
Global pattern of persistent human papillomavirus infection in female genital tract: An update system review and meta-analysis
Ming Zhao, Peipei Kang, Liling Zhu, Dan Zhou, Meimei Cui, Min Zhang, Jingjing Jia, Limei Luo
iScience.2024; 27(10): 110991. CrossRef
Analysis of Human Papilloma Virus Infection and Genotype in 336 Patients
秋培谭
Hans Journal of Biomedicine.2023; 13(02): 184. CrossRef
Characteristic of persistent human papillomavirus infection in women worldwide: a meta–analysis
Ming Zhao, Dan Zhou, Min Zhang, Peipei Kang, Meimei Cui, Liling Zhu, Limei Luo
PeerJ.2023; 11: e16247. CrossRef
Factors associated with persistence and clearance of HPV16/18 among rural Chinese women: a cohort study in Wufeng, Hubei province
Shuqi Pan, Wenshuang Wei, Xueying Du, Zhi Li, Jiyu Tuo, Min Zhang, Qing Liu
Women & Health.2022; 62(4): 276. CrossRef
Lactobacillus crispatus M247 oral administration: Is it really an effective strategy in the management of papillomavirus-infected women?
Miriam Dellino, Eliano Cascardi, Antonio Simone Laganà, Giovanni Di Vagno, Antonio Malvasi, Rosanna Zaccaro, Katia Maggipinto, Gerardo Cazzato, Salvatore Scacco, Raffaele Tinelli, Alessandro De Luca, Marina Vinciguerra, Vera Loizzi, Antonella Daniele, Ett
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Alternative New Mono-scaled Quantitative Benefit–Risk Assessment of Human Papillomavirus Vaccine in Japan
Tomoko Matsumoto, Naoki Matsumaru, Paul Scuffham, Pieter Neels, Katsura Tsukamoto
Therapeutic Innovation & Regulatory Science.2021; 55(1): 48. CrossRef
Next‐generation sequencing for typing human papillomaviruses and predicting multi‐infections and their clinical symptoms
Sang‐Yeon Kim, Kyung‐A Hwang, Ji‐Hoon Ann, Ji‐Hye Kim, Jae‐Hwan Nam
Microbiology and Immunology.2021; 65(7): 273. CrossRef
Association of age and viral factors with high-risk HPV persistence: A retrospective follow-up study
Wending Li, Yifan Meng, Yi Wang, Xiaodong Cheng, Chen Wang, Songshu Xiao, Xiaofei Zhang, Zaixing Deng, Mengjun Hu, Pingrong Shen, Shengfeng Xu, Chenglin Fu, Wen Jiang, Bing Wu, Kezhen Li, Gang Chen, Juncheng Wei, Ling Xi, Junbo Hu, Ding Ma, Min Xue, Xing
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Prevalence of HPV Among HIV-Negative Women of Child-Bearing Age in Lomé, Togo
Yawo Tufa Nyasenu, Fifonsi A Gbeasor-Komlanvi, Sabi Abdul-Raouf Issa, Amivi Ehlan, Martin Kouame Tchankoni, Brice M Yambiyo, Mireille Prince-David, Mounerou Salou, Didier K Ekouevi, Anoumou Dagnra
Future Virology.2019; 14(12): 783. CrossRef

11,793 View
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BCL2 Regulation according to Molecular Subtype of Breast Cancer by Analysis of The Cancer Genome Atlas Database: Ki-Tae Hwang, Kwangsoo Kim, Ji Hyun Chang, Sohee Oh, Young A Kim, Jong Yoon Lee, Se Hee Jung, In Sil Choi; Cancer Res Treat. 2018;50(3):658-669. Published online July 4, 2017; DOI: https://doi.org/10.4143/crt.2017.134

Abstract PDF Supplementary Material PubReader ePub

Purpose
We investigated B-cell lymphoma 2 (BCL2) regulation across DNA, RNA, protein, and methylation status according to molecular subtype of breast cancer using The Cancer Genome Atlas (TCGA) database.
Materials and Methods
We analyzed clinical and biological data on 1,096 breast cancers from the TCGA database. Biological data included reverse phase protein array (RPPA), mRNA sequencing (mRNA-seq), mRNA microarray, methylation, copy number alteration linear, copy number alteration nonlinear, and mutation data.
Results
The luminal A and luminal B subtypes showed upregulated expression of RPPA and mRNAseq and hypomethylation compared to the human epidermal growth factor receptor 2 (HER2) and triple-negative subtypes (all p < 0.001). No mutations were found in any subjects. High mRNA-seq and high RPPA were strongly associated with positive estrogen receptor, positive progesterone receptor (all p < 0.001), and negative HER2 (p < 0.001 and p=0.002, respectively). Correlation analysis revealed a strong positive correlation between protein and mRNA levels and a strong negative correlation between methylation and protein and mRNA levels (all p < 0.001). The high BCL2 group showed superior overall survival compared to the low BCL2 group (p=0.006).
Conclusion
The regulation of BCL2 was mainly associated with methylation across the molecular subtypes of breast cancer, and luminal A and luminal B subtypes showed upregulated expression of BCL2 protein, mRNA, and hypomethylation. Although copy number alteration may have played a minor role, mutation status was not related to BCL2 regulation. Upregulation of BCL2 was associated with superior prognosis than downregulation of BCL2.

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Elham Amjad, Babak Sokouti
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Maiquidieli Dal Berto, Laura Martin Manfroi, Aniúsca Vieira dos Santos, Giovana Tavares dos Santos, Gabriela Krüger da Costa, Camila Macedo Boaro, Péttala Rigon, Rafael José Vargas Alves, Claudia Giuliano Bica
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Ki-Tae Hwang, Young A. Kim, Jongjin Kim, Hyeon Jeong Oh, Jeong Hwan Park, In Sil Choi, Jin Hyun Park, Sohee Oh, Ajung Chu, Jong Yoon Lee, Kyu Ri Hwang
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Young Ju Jeong, Hoon Kyu Oh, Hye Ryeon Choi, Sung Hwan Park
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Case Report

Coexistence of VHL Disease and CPT2 Deficiency: A Case Report: Alfonso Massimiliano Ferrara, Monica Sciacco, Stefania Zovato, Silvia Rizzati, Irene Colombo, Francesca Boaretto, Maurizio Moggio, Giuseppe Opocher; Cancer Res Treat. 2016;48(4):1438-1442. Published online March 25, 2016; DOI: https://doi.org/10.4143/crt.2015.450

Abstract PDF PubReader ePub

von Hippel-Lindau (VHL) disease is an inherited syndrome manifesting with benign and malignant tumors. Deficiency of carnitine palmitoyltransferase type II (CPT2) is a disorder of lipid metabolism that, in the muscle form, manifests with recurrent attacks of myalgias often associated with myoglobinuria. Rhabdomyolytic episodes may be complicated by life-threatening events, including acute renal failure (ARF). We report on a male patient who was tested, at 10 years of age, for VHL disease because of family history of VHL. He was diagnosed with VHL but without VHL-related manifestation at the time of diagnosis. During childhood, the patient was hospitalized several times for diffuse muscular pain, muscle weakness, and dark urine. These recurrent attacks of rhabdomyolysis were never accompanied by ARF. The patient was found to be homozygous for the mutation p.S113L of the CPT2 gene. To the best of our knowledge, this is the first report of the coexistence of VHL disease and CPT2 deficiency in the same individual. Based on findings from animal models, the case illustrates that mutations in the VHL gene might protect against renal damage caused by CPT2 gene mutations.

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Original Articles

The Impact of High-Risk HPV Genotypes Other Than HPV 16/18 on the Natural Course of Abnormal Cervical Cytology: A Korean HPV Cohort Study: Kyeong A So, Mi Jung Kim, Ki-Heon Lee, In-Ho Lee, Mi Kyung Kim, Yoo Kyung Lee, Chang-Sun Hwang, Mi Seon Jeong, Mee-Kyung Kee, Chun Kang, Chi Heum Cho, Seok Mo Kim, Sung Ran Hong, Ki Tae Kim, Won-Chul Lee, Jong Sup Park, Tae Jin Kim; Cancer Res Treat. 2016;48(4):1313-1320. Published online March 9, 2016; DOI: https://doi.org/10.4143/crt.2016.013

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to evaluate the impact of high-risk human papillomaviruses (HPVs) other than HPV 16/18 on the natural course of atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL).
Materials and Methods
The study population was derived from the Korean HPV cohort (2010-2014). Women aged 20 to 60 who satisfied the criteria of having both HPV infection and abnormal cervical cytology of either ASC-US or LSIL were recruited from five institutions nationwide. Enrolled patients underwent cervical cytology and HPV DNA testing every 6 months.
Results
A total of 1,158 patients were enrolled. The 10 most common HPV types were HPV 16 (12.3%), 58 (10.0%), 56 (8.8%), 53 (8.4%), 52 (7.7%), 39 (6.2%), 18 (6.0%), 51 (5.7%), 68 (5.1%), and 66 (4.6%). Among these patients, 636 women were positive for high-risk HPVs other than HPV 16 or 18, and 429 women were followed for more than 6 months. Cytology evaluations showed progression in 15.3% of women, no change in 22.6%, and regression in 62.1% of women at 12 months. In cases of HPV 58 single infection, a more highly significant progression rate, compared to other high-risk types, was observed at 6 months (relative risk [RR], 3.3; 95% confidence interval [CI], 2.04 to 5.30; p < 0.001) and 12 months (RR, 5.03; 95% CI, 2.56 to 9.91; p < 0.001).
Conclusion
HPV genotypes numbered in the 50s were frequent in Korean women with ASC-US and LSIL. HPV 58 was the second most common type, with a high progression rate of cervical cytology.

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Women 50 Years and Older With Negative Pap Test and Positive Human Papillomavirus Test for Genotypes Other Than 16 and 18—Follow-up Outcomes
Farah S. Baban, Michael R. Henry, Margaret E. Long, Meredith A. VandeHaar, Grant M. Spears, Sarah M. Jenkins, Diva R. Salomao
Journal of Lower Genital Tract Disease.2024; 28(1): 43. CrossRef
Cervical intraepithelial neoplasia in non-16/18 high-risk human papilloma virus positive/cytology negative women: An alternative approach in poor resource areas
Fariba Yarandi, Elham Shirali, Elham Feizabad, Sara Ramhormoziyan, Soheila Sarmadi, Maryam SadrAmeli, Elham Arshadi
Taiwanese Journal of Obstetrics and Gynecology.2023; 62(2): 299. CrossRef
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Fatema Alzahraa Samy Amin, Zeba Un Naher, P. Shaik Syed Ali
Journal of Cancer Research and Clinical Oncology.2023; 149(10): 8077. CrossRef
Herpes Simplex Virus, Human Papillomavirus, and Cervical Cancer: Overview, Relationship, and Treatment Implications
Daniel Sausen, Oren Shechter, Elisa Gallo, Harel Dahari, Ronen Borenstein
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Association strength of E6 to E6AP/p53 complex correlates with HPV‐mediated oncogenesis risk
Matheus Vitor Ferreira Ferraz, Isabelle Freire Tabosa Viana, Danilo Fernandes Coêlho, Carlos Henrique Bezerra da Cruz, Maíra de Arruda Lima, Madson Allan de Luna Aragão, Roberto Dias Lins
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Serdar Aydın, Hande Nur Öncü, Dilek Sema Arıcı
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Rachelle P. Mendoza, Tahmineh Haidary, Elmer Gabutan, Ying Yin Zhou, Zaheer Bukhari, Courtney Connelly, Wen-Ching Lee, Yi-Chun Lee, Raj Wadgaonkar, Raag Agrawal, M. A. Haseeb, Raavi Gupta
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Sabrina S Plitt, Ryan Kichuk, Sheena Geier, Trenton Smith, Felicia Roy, Alberto Severini, Carmen L Charlton
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Tae-Kyu Jang, Jeong-Yeol Park, Dae-Yeon Kim, Dae-Shik Suh, Jong-Hyeok Kim, Yong-Man Kim, Young-Tak Kim, Joo-Hyun Nam
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Locoregional Recurrence by Tumor Biology in Breast Cancer Patients after Preoperative Chemotherapy and Breast Conservation Treatment: Eunjin Jwa, Kyung Hwan Shin, Ja Young Kim, Young Hee Park, So-Youn Jung, Eun Sook Lee, In Hae Park, Keun Seok Lee, Jungsil Ro, Yeon-Joo Kim, Tae Hyun Kim; Cancer Res Treat. 2016;48(4):1363-1372. Published online February 18, 2016; DOI: https://doi.org/10.4143/crt.2015.456

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to determine whether breast cancer subtype can affect locoregional recurrence (LRR) and ipsilateral breast tumor recurrence (IBTR) after neoadjuvant chemotherapy (NAC) and breast-conserving therapy (BCT). Materials and Methods We evaluated 335 consecutive patients with clinical stage II-III breast cancer who received NAC plus BCT from 2002 to 2009. Patients were classified according to six molecular subtypes: luminal A (hormone receptor [HR]+/HER2–/Ki-67 < 15%, n=113), luminal B1 (HR+/HER2–/Ki-67 ≥ 15%, n=33), luminal B2 (HR+/HER2+, n=83), HER2 with trastuzumab (HER2[T+]) (HR–/HER2+/use of trastuzumab, n=14), HER2 without trastuzumab (HER2[T–]) (HR–/HER2+, n=31), and triple negative (TN) (HR–/HER2–, n=61).
Results
After a median follow-up period of 7.2 years, 26 IBTRs and 37 LRRs occurred. The 5-year LRR-free survival rates were luminal A, 96.4%; B1, 93.9%; B2, 90.3%; HER2(T+), 92.9%; HER2(T–), 78.3%; and TN, 79.6%. The 5-year IBTR-free survival rates were luminal A, 97.2%; B1, 93.9%; B2, 92.8%; HER2(T+), 92.9%; HER2(T–), 89.1%; and TN, 84.6%. In multivariate analysis, HER2(T–) (IBTR: hazard ratio, 4.2; p=0.04 and LRR: hazard ratio, 7.6; p < 0.01) and TN subtypes (IBTR: hazard ratio, 6.9; p=0.01 and LRR: hazard ratio, 8.1; p < 0.01) were associated with higher IBTR and LRR rates. A pathologic complete response (pCR) was found to show correlation with better LRR and a tendency toward improved IBTR controls in TN patients (IBTR, p=0.07; LRR, p=0.03). Conclusion The TN and HER2(T–) subtypes predict higher rates of IBTR and LRR after NAC and BCT. A pCR is predictive of improved IBTR or LRR in TN subtype.

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The Clinical Impact of 21-Gene Recurrence Score on Treatment Decisions for Patients with Hormone Receptor-Positive Early Breast Cancer in Korea: Moo Hyun Lee, Wonshik Han, Jeong Eon Lee, Ku Sang Kim, Heeseung Park, Jongjin Kim, Soo Youn Bae, Hyun Joo Shin, Jong Won Lee, Eun Sook Lee; Cancer Res Treat. 2015;47(2):208-214. Published online September 11, 2014; DOI: https://doi.org/10.4143/crt.2013.223

Abstract PDF PubReader ePub

Purpose
The 21-gene (Oncotype DX) recurrence score (RS) assay is useful in predicting the benefits of adjuvant chemotherapy for early breast cancer patients and is widely used in Western countries. However, to date, it has not gained much popularity in East Asia. We analyzed the results from five institutions’ experience from using the 21-gene assay and examined the impact of assay results on decision making of chemotherapy in Korean breast cancer patients and the associations between RS and clinicopathologic characteristics.
Materials and Methods
The 21-gene assay was performed on 212 patients with estrogen receptor-positive early breast cancer in five institutions. Each center made systemic treatment decisions both before and after the knowledge of assay results.
Results
Among the 212 patients, 132 (62.3%) had a low RS of < 18, 60 (28.3%) had an intermediate RS of 18-30, and 20 (9.4%) had a high RS of ≥ 31. Histologic grade, presence of micrometastases, Ki-67, and presence of lymphatic invasion were statistically associated with the RS results. Treatment decisions were changed in 115 of 212 patients (54.2%) in 109 of 212 (51.4%) from chemotherapy plus hormone therapy to hormone therapy, and in six of 212 (2.8%) from hormone therapy to chemotherapy plus hormone therapy.
Conclusion
The 21-gene breast cancer assay proved to have a significant impact on treatment decision- making. The test reduces chemotherapy use in more than 50% of Korean estrogen receptor-positive, early breast cancer patients.

Citations

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Case Report

Case Series of Different Onset of Skin Metastasis According to the Breast Cancer Subtypes: Junhyeon Cho, Yohan Park, Jong-Chan Lee, Woo Jin Jung, Soohyeon Lee; Cancer Res Treat. 2014;46(2):194-199. Published online April 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.2.194

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We report on five cases of skin metastasis according to the breast cancer (BC) subtype. Two cases of HER2 positive BC showed only skin metastasis after immediate postoperative period and rapid clinical response to targeted therapy. Another two cases of triple negative BC showed thyroid and lung metastasis in addition to skin metastasis, and their response of cytotoxic chemotherapy was not definite. The other hormone positive BC showed skin metastasis only, with a longer, slower, less progressive pattern than other subtypes. Most cases of skin metastasis were detected at terminal stage of malignancy and were considered to have a limited survival period. However, some BC patients can survive longer if the targeted agents are effective. Therefore, physicians should provide detailed follow up of BC after curative treatment and understand the metastatic pattern of BC according to the subtype.

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Kristóf Attila Kovács, Csaba Kerepesi, Dalma Rapcsák, Lilla Madaras, Ákos Nagy, Anikó Takács, Magdolna Dank, Gyöngyvér Szentmártoni, Attila Marcell Szász, Janina Kulka, Anna Mária Tőkés
Scientific Reports.2025;[Epub] CrossRef
Cutaneous Metastasis of Triple Negative Breast Cancer: A Case Report and Review of Literature
Stefanos Flindris, Chrysoula Margioula-Siarkou, Georgia Margioula-Siarkou, Chrysoula Gouta, Effrosyni Styliara, Iordanis Navrozoglou, Konstantinos Dinas, Stamatios Petousis
Cureus.2025;[Epub] CrossRef
Topical TLR7 agonist and radiotherapy in patients with metastatic breast cancer
Sylvia Adams, Sandra Demaria, Darawan Rinchai, Ena Wang, Yelena Novik, Ruth Oratz, Maria Fenton-Kerimian, Pascale G Levine, Xiaochun Li, Francesco Marincola, Ping Jin, David Stroncek, Judith Goldberg, Davide Bedognetti, Silvia Chiara Formenti
Journal for ImmunoTherapy of Cancer.2025; 13(4): e011173. CrossRef
Isolated Axillary Skin Recurrence as the First Sign of Breast Cancer Relapse 20 Years After Initial Treatment: A Case Report
Hye Un Ma, Yong Min Na, Hee Won Ryu, Sang Ho Jo, Young Jae Ryu, Sang Chun Park, Yong Bin Kwon, Jin Seong Cho, Ji Shin Lee, Min Ho Park
Journal of Breast Disease.2025; 13(1): 9. CrossRef
Five-Fraction High-Conformal Ultrahypofractionated Radiotherapy for Primary Tumors in Metastatic Breast Cancer
Jeongshim Lee, Jee Hung Kim, Mitchell Liu, Andrew Bang, Robert Olson, Jee Suk Chang
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Nam Hee Koh, Ha Yeun Oh
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Cutaneous Metastasis in Breast Cancer: A Case Series
Neelesh Shrivastava, A Balasubramanian
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Zhong-Hui Li, Fang Wang, Ping Zhang, Peng Xue, Shi-Jie Zhu
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Sara Wilchowski
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Frontiers in Oncology.2021;[Epub] CrossRef
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Ajinkya Sawant, Sumit Kar, Safa Patrick, Nitin Gangane
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Exuberant case of cutaneous metastasis of breast cancer
Vítor Angelo Ferreira, Karla Spelta, Lucia Martins Diniz, Elton Almeida Lucas
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Original Articles

An Association Study of Polymorphisms in JAK3 Gene with Lung Cancer in the Korean Population: Wonbeak Yoo, Hae-Yun Jung, Seungjoon Lim, Jae Sook Sung, Kyong Hwa Park, Jeong Seon Ryu, Sang Won Shin, Jun Suk Kim, Jae Hong Seo, Yeul Hong Kim; Cancer Res Treat. 2011;43(2):108-116. Published online June 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.2.108

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PURPOSE
The genetic alteration of the janus kinases (JAKs), non-receptor tyrosine kinase, is related to the development of human cancers. However, little is known about how the sequence variation of JAK3 contributes to the development of lung cancer. This study investigated whether polymorphisms at the promoter region of the JAK3 gene are associated with the risk of lung cancer in the Korean population.
MATERIALS AND METHODS
A total of 819 subjects, including 409 lung cancer patients and 410 healthy controls were recruited. The SNaPshot assay and polymerase chain reaction-restriction fragment length polymorphism analysis were used, and logistic regression analyses were performed to characterize the association between polymorphisms of JAK3 and lung cancer risk.
RESULTS
Three polymorphisms (-672 G>A, +64 A>G and +227 G>A) of JAK3 were analyzed for large-scale genotyping (n=819). Statistical analyses revealed that polymorphisms and haplotypes in the JAK3 gene were not significantly associated with lung cancer.
CONCLUSION
JAK3 gene was not significantly associated with the risk of lung cancer in the Korean population.

Citations

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Association Analysis of Polymorphic Gene Variants in the JAK/STAT Signaling Pathway with Aging and Longevity
V. V. Erdman, T. R. Nasibullin, I. A. Tuktarova, R. Sh. Somova, O. E. Mustafina
Russian Journal of Genetics.2019; 55(6): 728. CrossRef

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Association of Single Nucleotide Polymorphisms in PIM-1 Gene with the Risk of Korean Lung Cancer: Dae Sik Kim, Jae Sook Sung, Eun Soon Shin, Jeong-Seon Ryu, In Keun Choi, Kyong Hwa Park, Yong Park, Eui Bae Kim, Seh Jong Park, Yeul Hong Kim; Cancer Res Treat. 2008;40(4):190-196. Published online December 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.4.190

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Purpose

The expression of the PIM-1 gene, which is a proto-oncogene that encodes a serine/threonine kinase, is associated with multiple cellular functions such as proliferation, differentiation, apoptosis and tumorigenesis. In particular, several studies have reported that the PIM-1 gene is associated with the development of lymphoma, leukemia and prostate cancer. Therefore, this study was conducted to evaluate the association between the single nucleotide polymorphisms in the PIM-1 gene and the risk of lung cancer occurrence in the Korean population.

Materials and Methods

To evaluate the role of the PIM-1 gene in the development of lung cancer, the genotypes of the PIM-1 gene were determined in 408 lung cancer patients and 410 normal subjects.

Results

We found that the T-C-T-C haplotypes of the PIM-1 gene (-1196 T>C, IVS4 +55 T>C, IVS4 +1416 T>A and +3684 C>A) were associated with an increased risk of lung cancer [adjusted odds ratio (aOR): 3.98; 95% CI: 1.24~12.75, p-value: 0.020]. In particular, these haplotypes showed an increased risk of lung cancer in males (aOR: 5.67; 95% CI: 1.32~24.30, p-value: 0.019) and smokers (aOR: 7.82; 95% CI: 1.75~34.98, p-value: 0.007).

Conclusions

The present results suggest that the T-C-T-C haplotype of the PIM-1 gene could influence the risk of developing smoking-related lung cancer in the Korean population. Additional functional studies with an larger sample sized analysis are warranted to reconfirm our findings.

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A review on structure-function mechanism and signaling pathway of serine/threonine protein PIM kinases as a therapeutic target
Ajaya Kumar Rout, Budheswar Dehury, Satya Narayan Parida, Sushree Swati Rout, Rajkumar Jena, Neha Kaushik, Nagendra Kumar Kaushik, Sukanta Kumar Pradhan, Chita Ranjan Sahoo, Ashok Kumar Singh, Meenakshi Arya, Bijay Kumar Behera
International Journal of Biological Macromolecules.2024; 270: 132030. CrossRef
Impact of Pim1 mutations on the survival outcomes of patients with breast cancer: Insights from a clinical study
Syed Sultan Beevi, Kavitha Anbrasu, Vinod Kumar Verma, Nagesh Kishan Panchal, Krishna Kiran Kannepalli, Raghu Ram Pillarisetti, Sailaja Madigubba, Jyotsana Dwivedi, Neha Damodar, Radhika Chowdary Darapuneni
Human Gene.2024; 40: 201295. CrossRef
HCG11 inhibits salivary adenoid cystic carcinoma by upregulating EphA2 via binding to miR-1297
Shujuan Yan, Meng Wang
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology.2023; 135(2): 257. CrossRef
Therapeutic targeting of PIM KINASE signaling in cancer therapy: Structural and clinical prospects
Aanchal Rathi, Dhiraj Kumar, Gulam Mustafa Hasan, Mohammad Mahfuzul Haque, Md Imtaiyaz Hassan
Biochimica et Biophysica Acta (BBA) - General Subjects.2021; 1865(11): 129995. CrossRef
Loss of PIM1 correlates with progression and prognosis of salivary adenoid cystic carcinoma (SACC)
Jiajie Xu, Xin Zhu, Qingling Li, Chao Chen, Zhenying Guo, Zhuo Tan, Chuanming Zheng, Minghua Ge
Cancer Cell International.2018;[Epub] CrossRef
PIM Kinase as an Executional Target in Cancer
Xinning Zhang, Mengqiu Song, Joydeb Kumar Kundu, Mee-Hyun Lee, Zhen-Zhen Liu
Journal of Cancer Prevention.2018; 23(3): 109. CrossRef
HistoneH3 demethylase JMJD2A promotes growth of liver cancer cells through up-regulating miR372
Jiahui An, Jie Xu, Jiao Li, Song Jia, Xiaonan Li, Yanan Lu, Yuxin Yang, Zhuojia Lin, Xiaoru Xin, Mengying Wu, Qidi Zheng, Hu Pu, Xin Gui, Tianming Li, Dongdong Lu
Oncotarget.2017; 8(30): 49093. CrossRef
Expressions of osteopontin (OPN), ανβ3 and Pim-1 associated with poor prognosis in non-small cell lung cancer (NSCLC)
Yi Jin, Da-yue Tong, Lu-ying Tang, Jian-ning Chen, Jing Zhou, Zhi-ying Feng, Chun-kui Shao
Chinese Journal of Cancer Research.2012; 24(2): 103. CrossRef
Overexpression of Osteopontin, αvβ3 and Pim-1 Associated with Prognostically Important Clinicopathologic Variables in Non-Small Cell Lung Cancer
Yi Jin, Da-yue Tong, Jian-ning Chen, Zhi-ying Feng, Jian-yong Yang, Chun-kui Shao, Jia-ping Li, Rossella Rota
PLoS ONE.2012; 7(10): e48575. CrossRef
No Association between PIK3CA Polymorphism and Lung Cancer Risk in the Korean Population
Jae-Sook Sung, Kyong-Hwa Park, Seung-Tae Kim, Jae-Hong Seo, Sang-Won Shin, Jun-Suk Kim, Yeul-Hong Kim
Genomics & Informatics.2010; 8(4): 194. CrossRef

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Clinicopathological Analysis of Borrmann Type IV Gastric Cancer: Jeong Hwan Yook, Sung Tae Oh, Byung Sik Kim; Cancer Res Treat. 2005;37(2):87-91. Published online April 30, 2005; DOI: https://doi.org/10.4143/crt.2005.37.2.87

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Purpose

Borrmann type IV gastric cancer is often diagnosed only at an advanced stage, resulting in a prognosis poor. We performed a retrospective study of the clinical characteristics of Borrmann type IV gastric cancer and the prognostic factors affecting the survival rate in such patients.

Materials and Methods

Of 4,063 patients with all gastric cancers, 370 (9%) with Borrmann type IV gastric cancer were analyzed.

Results

The clinical characteristics of these patients included a higher incidence rate in young females, and higher rates of serosa exposure, metastasis to lymph nodes and early peritoneal dissemination. Of patients presenting with peritoneal seeding, those resected had a higher survival rate than those that were not. A univariate analysis showed that the prognostic factors affecting the survival rate following a curative resection were the location, occupied area and depth of the primary tumor, as well as the presence of lymph node metastasis and the tumor stage. A multivariate analysis indicated that the tumor location and stage were significant independent prognostic factors after a curative resection for Borrmann type IV gastric cancer.

Conclusion

In conclusion, the early diagnosis and treatment of patients with Borrmann type IV gastric cancer are essential for the better survival of these patients. Even in patients with advanced tumors, a noncurative palliative resection may improve the prognosis.

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Mira Yoo, Yoon Kong, Guan Hong Min, Du-Yeong Hwang, So Hyun Kang, Young Suk Park, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Yun-Suhk Suh
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Borrmann Type IV Gastric Cancer: Computed Tomography Features and Corresponding Pathological Findings
Changfeng Ji, Yi Ma, Zhong Zheng, Song Liu, Zhengyang Zhou
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Clinicopathological and prognostic features of Borrmann type IV gastric cancer versus other Borrmann types: A unique role of signet ring cell carcinoma
Chengcai Liang, Yao Liang, Biyi Ou, Lei Yuan, Shuqiang Yuan
Saudi Journal of Gastroenterology.2023; 29(4): 240. CrossRef
PN3b as an independent risk factor for poor prognosis and peritoneal recurrence in Borrmann type IV gastric cancer: A retrospective cohort study
Yiran Chen, Yanyan Chen, Liping Wen, Laizhen Tou, Haiyong Wang, Lisong Teng
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Comparative Outcomes of Laparoscopic Gastrectomy and Open Gastrectomy for Scirrhous Gastric Cancer: A Multicenter Retrospective Cohort Study
Yusuke Fujita, Tatsuto Nishigori, Yoshio Kadokawa, Atsushi Itami, Masato Kondo, Hisahiro Hosogi, Seiichiro Kanaya, Hironori Kawada, Hiroaki Hata, Michihiro Yamamoto, Yousuke Kinjo, Eiji Tanaka, Dai Manaka, Seiji Satoh, Hiroshi Okabe, Shigeru Tsunoda, Masa
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Chengcai Liang, Guoming Chen, Baiwei Zhao, Haibo Qiu, Wei Li, Xiaowei Sun, Zhiwei Zhou, Yingbo Chen
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Hai-Bo Huang, Zi-Ming Gao, An-Qi Sun, Wei-Tian Liang, Kai Li
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Makiko Yasumoto, Etsuko Sakamoto, Sachiko Ogasawara, Taro Isobe, Junya Kizaki, Akiko Sumi, Hironori Kusano, Jun Akiba, Takuji Torimura, Yoshito Akagi, Hiraku Itadani, Tsutomu Kobayashi, Shinichi Hasako, Masafumi Kumazaki, Shinji Mizuarai, Shinji Oie, Hiro
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Borrmann type IV gastric cancer should be classified as pT4b disease
Jin-yu Huang, Zhen-ning Wang, Chun-yang Lu, Zhi-feng Miao, Zhi Zhu, Yong-xi Song, Hui-mian Xu, Ying-ying Xu
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Syed A. Ahmad, Brent T. Xia, Christina E. Bailey, Daniel E. Abbott, Beth A. Helmink, Meghan C. Daly, Ramya Thota, Cameron Schlegal, Leah K. Winer, S. Ameen Ahmad, Ali H. Al Humaidi, Alexander A Parikh
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Fang-Qing Zhu, Hong-Jin Chu, Zhao-Hua Gong, Feng-Cai Du, Jian Chen, Li-Xin Jiang
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Ji Young Chang, Ki-Nam Shim, Chung Hyun Tae, A Reum Choe, Chang Mo Moon, Seong-Eun Kim, Hye-Kyung Jung, Sung-Ae Jung
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Survival Benefit of Palliative Gastrectomy in Gastric Cancer Patients with Peritoneal Metastasis
Masanori Tokunaga, Masanori Terashima, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Hirofumi Yasui, Narikazu Boku
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Risk Stratification for Serosal Invasion Using Preoperative Predictors in Patients with Advanced Gastric Cancer
Sung-Sil Park, Jae-Seok Min, Kyu-Jae Lee, Sung-Ho Jin, Sunhoo Park, Ho-Yoon Bang, Hwang-Jong Yu, Jong-Inn Lee
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Jae Bong Ahn, Tae Kyung Ha, Hang Rak Lee, Sung Joon Kwon
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Hubert Scheidbach, Hans Lippert, Frank Meyer
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Hyun Il Kim, Tae Kyung Ha, Sung Joon Kwon
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Prognosis of pN3 Stage Gastric Cancer
Jung Ryun Ahn, Minkyu Jung, Chan Kim, Min Hee Hong, Hong Jae Chon, Hye Ryun Kim, Hei-Cheul Jeung, Woo Jin Hyung, Sung Sook Lee, Hyun Cheol Chung, Sung Hoon Noh, Sun Young Rha
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Borrmann Type IV: An Independent Prognostic Factor for Survival in Gastric Cancer
Ji Yeong An, Tae Ho Kang, Min Gew Choi, Jae Hyung Noh, Tae Sung Sohn, Sung Kim
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Prognostic Factors for Advanced Gastric Cancer: Stage-stratified Analysis of Patients who Underwent Curative Resection
Joong-Min Park, Woo-Sang Ryu, Jong-Han Kim, Sung-Soo Park, Seung-Joo Kim, Chong-Suk Kim, Young-Jae Mok
Cancer Research and Treatment.2006; 38(1): 13. CrossRef

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Overexpression of c-met Protein in Gastric Cancer and Role of uPAR as a Therapeutic Target: Hyun A Oh, Gu Lee, Hee Jung Kang, Yong Gil Kim, Sung Hwa Bae, Jae Lyun Lee, Kyung Hee Lee, Myung Soo Hyun, Dong Suk Kim; Cancer Res Treat. 2003;35(1):9-15. Published online February 28, 2003; DOI: https://doi.org/10.4143/crt.2003.35.1.9

Abstract PDF

PURPOSE
One of the members of the tyrosine kinase receptor family is the protein product of the c-met proto-oncogene, which is the receptor for hepatocyte growth factor (HGF). HGF is known as a potent mitogen and motogen for many kinds of carcinoma cells, and has been found to simulate the growth and progression of gastric cancer cells through HGF-receptors. In addition, the urokinase-type plasminogen activator (uPA) and receptor (uPAR) also play important roles in the invasion and metastasis. MATERIALS AND METHODS: The expression of c-met protein was investigated using immunohistochemical staining of 50 paraffin embedded gastric cancers, and by measuring the serum uPAR levels, before and after an operation, in gastric cancer patients using an ELISA assay. RESULTS: Of the 50 cases, 32 (64%) expressed the c-met protein. The c-met protein expression was significantly correlated with the TNM staging (p<0.05), but the other prognostic factors were not significant variables. According to a Kaplan-Meier's plot, the one and three year overall survival rates were 94 and 70% in patients not expressing the c-met protein, and 81 and 33% in those that did, and the Survival curves revealed a significantly different prognosis (p=0.04). Elevated serum uPAR levels (> or=3257.8 pg/ml, control+/-mean 2SD) were observed in 9 (34.6%) of 26 gastric cancer patients, but in none of control subjects. Average serum uPAR levels were 2980.8+/-616.2 pg/ml before the operation and 2404.7+/-455.9 pg/ml after, and decreased significantly after surgical resection (p<0.05). The serum uPAR level correlated significantly with lymph node metastasis and vessel invasion (p<0.05) CONCLUSION: The expression of c-met protein, and the level of uPAR, may be prognostic factors in gastric cancer.

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Rational Design and In Silico Evaluation of a Multiepitope Vaccine Targeting the uPAR for Cancer Immunotherapy
Fahimeh Baghaei, Zahra Hemmat, Amir Taherkhani, Setareh Shojaei, Ali Teimoori, Poorani Gurumallesh
Journal of Immunology Research.2025;[Epub] CrossRef
Ferroptosis regulating lipid peroxidation metabolism in the occurrence and development of gastric cancer
Lan-Mei Wang, Wei-Wei Zhang, Ying-Yang Qiu, Fang Wang
World Journal of Gastrointestinal Oncology.2024; 16(6): 2781. CrossRef
Research progress on the development of hepatocyte growth factor/c-Met signaling pathway in gastric cancer: A review
Wu-Jie Wei, Ya-Li Hong, Yi Deng, Guan-Liang Wang, Jiang-Tao Qiu, Fang Pan
World Journal of Gastrointestinal Oncology.2024; 16(8): 3397. CrossRef
Human Triosephosphate Isomerase Is a Potential Target in Cancer Due to Commonly Occurring Post-Translational Modifications
Sergio Enríquez-Flores, Ignacio De la Mora-De la Mora, Itzhel García-Torres, Luis A. Flores-López, Yoalli Martínez-Pérez, Gabriel López-Velázquez
Molecules.2023; 28(16): 6163. CrossRef
SMYD3 Modulates the HGF/MET Signaling Pathway in Gastric Cancer
Katia De Marco, Martina Lepore Signorile, Elisabetta Di Nicola, Paola Sanese, Candida Fasano, Giovanna Forte, Vittoria Disciglio, Antonino Pantaleo, Greta Varchi, Alberto Del Rio, Valentina Grossi, Cristiano Simone
Cells.2023; 12(20): 2481. CrossRef
MET in gastric cancer with liver metastasis: The relationship between MET amplification and Met overexpression in primary stomach tumors and liver metastasis
Han S. Kim, Hong J. Chon, Hyunki Kim, Su‐Jin Shin, Volker Wacheck, Aaron M. Gruver, Jong S. Kim, Sun Y. Rha, Hyun C. Chung
Journal of Surgical Oncology.2018; 117(8): 1679. CrossRef
Hepatocyte growth factor induced up-regulations of VEGF through Egr-1 in hepatocellular carcinoma cells
Kyung Hee Lee, Jae-Ryong Kim
Clinical & Experimental Metastasis.2009; 26(7): 685. CrossRef
Association of Extracellular Cleavage of E-Cadherin Mediated by MMP-7 with HGF-Induced in vitro Invasion in Human Stomach Cancer Cells
K.H. Lee, E.Y. Choi, M.S. Hyun, B.I. Jang, T.N. Kim, S.W. Kim, S.K. Song, J.H. Kim, J.-R. Kim
European Surgical Research.2007; 39(4): 208. CrossRef

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SB203580, a P38 MAPK Inhibitor, Blocks in vitro Invasion by Human Gastric SNU-638 Cells: Ju Chae Park, Hyeon Gyeung Yoo, Hong Su Kim, Min A Jung, Mi Ha Kim, Sang Won Han, Kee Oh Chay, Boo Ahn Shin, Bong Whan Ahn, Young Do Jung; Cancer Res Treat. 2002;34(6):426-431. Published online December 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.6.426

Abstract PDF

PURPOSE
The role of P38 mitogen-activated protein kinase (MAPK) in gastric cancer invasion has not yet been determined. In this study, we examined the effects of SB203580, a specific P38 MAPK inhibitor, on the in vitro invasion of gastric cancer and upon the molecules involved in this process.
MATERIALS AND METHODS
Human gastric cancer SNU-638 cells were maintained in RPMI 1640 supplemented with 10% FBS. BIOCOAT matrigel invasion chambers were used to examine in vitro invasiveness, zymography for gelatinase activity, CAT assay for uPA promoter activity and Western and Northern blotting to determine protein and mRNA levels, respectively.
RESULTS
Treatment of SNU-638 cells with SB203580, a specific P38 MAPK inhibitor, reduced in vitro invasiveness, dose-dependently. SB203580 treatment was found to decrease both mRNA expression and uPA promoter activity in gastric SNU-638 cells. In vitro invasion of SNU-638 cells was partially abrogated by uPA-neutralizing antibodies. The activities of MMPs were not significantly altered by SB203580.
CONCLUSION
Our results suggest that P38 MAPK is a potential therapeutic target for inhibiting uPA-dependent gastric tumor invasiveness and metastasis.

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The Common Hallmarks and Interconnected Pathways of Aging, Circadian Rhythms, and Cancer: Implications for Therapeutic Strategies
Jie Wang, Fanglin Shao, Qing Xin Yu, Luxia Ye, Dilinaer Wusiman, Ruicheng Wu, Zhouting Tuo, Zhipeng Wang, Dengxiong Li, William C. Cho, Wuran Wei, Dechao Feng
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Shigeo Nagashima, Putu Prathiwi Primadharsini, Masaharu Takahashi, Takashi Nishiyama, Kazumoto Murata, Hiroaki Okamoto
Pathogens.2024; 13(12): 1130. CrossRef

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Membrane-type Matrix Metalloproteinase-1 Induced Invasive and Angiogenic Activities in Chick Chorioallantoic Membrane (CAM) Model: Joo Won Jeong, Tae Kwon Sohn, Dae Yeul Yu, Kyu Won Kim; J Korean Cancer Assoc. 2001;33(1):49-55.

Abstract PDF: PURPOSE
Matrix metalloproteinases (MMPs) have been reported to play critical roles in the endothelial cell migration and matrix remodeling during angiogenic process. To investigate the roles of the membrane type MMP (MT1-MMP) by the matrix remodeling of endothelial cells, MT1-MMP expression vector was transfected into bovine aortic endothelial cells (BAECs). Increased ex+pression of MT1-MMP in BAECs enhanced the activation of MMP-2, invasion and migration of BAECs. Moreover, the capacity of tube formation was increased by MT1-MMP transfectants. These observations indicate that MT1-MMP is involved in the angiogenic process of endothelial cells in vitro. In this study, we attempted these effects were confirmed in vivo system.
MATERIALS AND METHODS
In this study, we used MT1- MMP or Antisense MT1-MMP stable transfectants in HT1080 human fibrosarcoma cells. Chorioallantoic membrane (CAM) assay was used for the detection of angiogenesis in vivo and modified CAM assay for quantification of invasion of MT1-MMP transfected cells.
RESULTS
In CAM assay, the formation of microvessels was stimulated by MT1-MMP transfectants. Invasive capacity of HT1080 cells was also increased in a novel in vivo metastasis model, PCR based CAM assay.
CONCLUSION
These results identify the function of MT1- MMP during the neovascularization process.

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A Study of Relationship between the Progression and Subtypes of Gastric Adenocarcinoma and Fas - L / sFas - L: S C Lim, Y D Min; J Korean Cancer Assoc. 2000;32(2):288-296.

Abstract PDF: PURPOSE
The purpose of this study is to determine whether human gastric adenocarcinoma expresses Fas-L, whether serum sFas-L level is changed in patients before and after gastrectomy, and whether Fas-L or sFas-L is concerned in tumor stage and histologic type.
MATERIALS AND METHODS
The authors analysed 38 cases of early gastric carcinoma (EGC) and 61 cases of advanced gastric carcinoma (AGC) who received gastric resection from 1997 to 1998, in whom the number of diffuse type is 38 cases and the number of intestinal type is 61 cases. The authors used immunohistochemical staining for tumoral Fas-L detection and sFas ligand ELISA kit for serum sFas-L detection.
RESULTS
Fas-L was localized to neoplastic cells in 61% (23/38) cases of EGC group and 66% (40/61) cases of AGC group. The extent of Fas-L expression was variable, with both FasL- positive and -negative neoplastic region occuring within tumors. The mean serum sFas-L level was highly significantly higher in patients before treatment compared with controls, whereas in patients in post-gastrectomy was significantly lower as the level of controls. Some patients whose preoperative serum sFas-L levels were within normal limits expressed no tumoral Fas-L. In addition, factors such as tumor stage, histologic subtype and other prognostic factors were not concerned in Fas-L expression and serum sFas-L level.
CONCLUSION
The authors demonstrate a statistically significant expression of tumoral Fas-L with concomitant increment of serum sFas-L in gastric adenocarcinoma. This finding suggests Fas-mediated apoptosis in response to Fas-L expression by gastric adenocarcinoma, and provide the evidence to support the Fas counterattack and indicate that the serum sFas-L level is a useful indicator in evaluating preoperative diagnosis and postoperative follow-up of gastric adeno- carcinoma. In addition, every clinical stages of gastric adenocarcinoma of the intestinal and the diffuse type not differ in their expression of the Fas and sFas-L.

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Clinical Significance of Urokinase - type Plasminogen Activator Receptor ( uPAR ) Expression in Breast Cancer Tissues: Soo Jung Gong, Sun Young Rha, Hei Chul Jung, Joon Oh Park, Nae Choon Yoo, Jae Kyung Roh, Woo Ick Yang, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 2000;32(1):53-59.

Abstract PDF: PURPOSE
Cancer invasion is induced by several proteolytic enzyme systems associated with the destruction of basement membrane and extracellular matrix. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) have been reported as prognostic factors in breast cancer patients and plasminogen activation is regulated by various factor such as uPAR and growth factor. So we examined the tissue levels of urokinase-type plasminogen activator receptor (uPAR) in breast cancer patients.
MATERIALS AND METHODS
Tissue uPAR levels were measured by ELISA assay in 268 breast cancer patients.
RESULTS
The median and mean values of tissue uPAR level in breast cancer were 3.5 ng/mg and 4.8+-3.6 ng/mg cytosol protein, respectively. Tissue uPAR level was the highest in T1 stage, but there was no statistical significance between T stage (p >0.05). In nodal stage, there was also no difference in the value of uPAR according to progression. And the value of uPAR expression was not associated with estrogen and progesteron receptor status, number of involved node and percent of node involvement. In TNM stage, tissue uPAR levels were higher in patients with stage I-II than in patients with stage III-IV (p=0.027). In univariate analysis, nodal factor (p=0.0023) and TNM stage (p=0.0004) were significantly associated with overall survival. But, multivariate analysis showed that TNM stage was the only significant prognostic factor (p=0.0002). CONCLUSION: These results suggest that uPAR is mainly associated with initial tumor invasion and other factors might be involved in later stages of cancer progression.

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Clinical Analysis of the Favorable Type of Breast Cancer - Medullary , Mucinous , Papillary and Tubular Carcinoma: Chang Wan Jeon, Woo Chul Noh, Nan Mo Moon, Nam Sun Paik, Jong Inn Lee, Dong Wook Choi, Ho Yoon Bang; J Korean Cancer Assoc. 1999;31(1):82-89.

Abstract PDF: PURPOSE
The favorable types of the breast cancer - medullary, mucinous, papillary and tubular carcinoma are uncommon subtypes and their incidences in different series ranges between 2.0% and 8.0%, 1% and 2%, 0.3% and 3%, less than 2% of all breast cancers, respectively. In westem countries these subtypes have been reported to have good prognosis and slow growth rate. Clinically, these tumors have lower frequency of axillary nodal involvement and better 5-year or 10-year surviral rate than the other common types of breast cancer.
MATERIALS AND METHODS
To determine the clinical characteristics and to evaluate the correlation between the progrostic factors and survival rate of these tumors, the medical records of 83 women with medullary, mucinous, papillary and tubular carcinoma treated at Korea Cancer Center Hospital between Jan. 1987 and Dec. 1997 were reviewed retrospectively.
RESULTS
The incidences of medullary, mucinous, papillary and tubular carcinoma were 0.51%, 1.45%, 0.71% and 0.14% of all breast cancer, respectively. There were 1 case of local recurrence and 5 cases of systemic relapse during the follow-up (median follow-up peroid of 56 months). Overall 5-year survival and 10-year survival rate were 98.5% and 94.2%, respectively. No significant difference in overall survival rate was detected according to histologic types of these tumors but disease-free survival was significantly lower in papillary carcinoma than the other types of these tumors (p=0.042). Standard prognostic factors of breast cancer such as tumor size, lymph node status, age of the patient and ER status did not affect the prognosis of these tumors.
CONCLUSION
Medullary, mucinous, papillary and tubular carcinoma revealed very excellent prognosis in this study regardless of tumor size, lymph node status, age of the patients and ER status.

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Germline Mutations of the NF2 Gene in Korean Neurofibromatosis 2 Patient: Hee Jin Yang, Yong Jin Won, Kyu Joo Park, Hee Won Jung, Kil Soo Choi, Jae Gahb Park; J Korean Cancer Assoc. 1998;30(4):790-799.

Abstract PDF: PURPOSE
Neurofibromatosis 2(NF2) is an autosomal dominant disease characterized by development of bilateral acoustic neuroma and various central nervous system tumors such as meningiomas, ependymomas, and schwannomas. Recent cloning of the gene responsible for NF2, the NF2 gene, permits the presymptomatic genetic diagnosis of affected individuals by direct analysis of the gene. This paper was intended to identify germline mutations in Korean NF2 patients.
MATERIALS AND METHODS
We collected blood samples from 15 clinically diagnosed NF2 patients treated at the Department of Neurosurgery, Seoul National University Hospital. Purified genomic DNA samples were analyzed for mutations of the NF2 gene by using polymerase chain reaction(PCR)-single strand conformation polymorphism(SSCP) method followed by direct DNA sequencing.
RESULTS
We were able to identify germline mutation of the NF2 gene in one patient. The mutation identified was 1 base pair deletion(A) at codon 318, resulting in premature stop codon due to frameshift.
CONCLUSION
Identification of the germline mutation in NF2 gene should enable us to test all individual family members at risk to determine whether or not they carry the mutant NF2 gene.

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Effect on Malignant Phenotype of Gastric Cancer Cell Line after p53 Gene Transduction: Sun Young Rha, Tae Soo Kim, Sook Jung Jeong, Joong Bae Ahn, kwang Yong Shim, Soo Jung Kong, Hwa Young Lee, Nae Choon Yoo, Jin Hyuk Choi, Ho Young Lim, Joo Young Lim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(3):508-520.

Abstract PDF: PURPOSE
To evaluate the effect of wild type p53 gene transduction on the malignant phenotypes for metastasis in gastric cancer, we compared the biological phenpotypes of gastric cancer cell lines based on p53 gene status. Then, after retrovirus-mediated wild-type p53 gene transduction, we compared those phenotypes among parent YCC-3 cell line, vector transduced YCC-3v cell line and a clone of YCC-3C3. MATERIAL AND METHODS: Four human gastric cancer celi lines were used; YCC-l(mutant), YCC-2(wild), YCC-3(mutant) and AGS(wild). DNAs of the cell lines were analyzed to evaluate the mobility shift with PCR-SSCP. Tumorigenecity and proliferation were evaluated by soft agar assay and proliferation assay. Migratory capacity was measured by adhesion assay and Boyden chamber assay. p53 protein expression was measured by Western blot analysis and VEGF, WAF-1 were measured by ELISA assay. Angiogenic activity was measured by cross-feeding assay and cell cycle analysis was performed by flowcytometry. In vivo tumorigenicity was measured by xenograft in nude mice.
RESULTS
YCC-3 cell line with mutant p53 gene expressed all the phenotypes for the metastasis such as tumorigenicity, migration and angiogenesis. In a stable clone of YCC-3C3, no differences were found in proliferation, cell cycle and WAP-1 expression when compared to those of the control YCC-3v and parent YCC-3 cell line, even if increased p53 protein production was found by Western blot analysis. However, both in vitro and in vivo tumorigenicity were decreased in a stably transduced YCC-3C3 clone. The adhesive capacity was also decreased in YCC-3C3 clone whereas the endothelial cell growth stimulatory effect and VEGF production showed no difference compared to those of the YCC-3v cell line.
CONCLUSION
Wild-type p53 gene transduction in gastric cancer cell line decreased tumorigenicity which resulted from decreased colony forming activity and adhesive capacity but not formed changes of angiogenic activity. This suggested the possible application of anti- metastasis strategy with p53 gene therapy in gastric cancer.

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Restoration of Wild - type p53 Induces Chemo-sensitization in the Gastric Cancer Cell Line with Mutant p53: Ho Young Maeng, Sun Young Rha, Byung Soh Min, Yong Bae Kim, Hyun Joo Kwak, Tae Soo Kim, Kyu Hyun Park, Nae Choon Yoo, Ho Young Lim, Jin Hyuk Choi, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(3):497-507.

Abstract PDF: PURPOSE
It has been theorized that p53 may be involved in the sensitivity to chemotherapeutic agents. We evaluated the chemosensitivity of wild p53 after transduction into gastric cancer cell lines with mutant p53.
MATERIALS AND METHODS
YCC-3(parent cell line with mutant p53), YCC-3v(parent cell line transduced with vector alone) and YCC-3C3(clone with wild p53) cell lines were used in this study. p53 protein expression was measured by ELISA assay. Tumorigenicity and drug sensitivity were evaluated by soft agar and proliferation assay, respectively. Cell cycle analysis was performed by flowcytometry. Telomerase activity was measured by TRAP assay and terminal restriction fragment(TRF) length was measured after Southern blot analysis.
RESULTS
Even though p53 production from the YCC-3C3 cell line was three times higher than those of YCC-3 and YCC-3v cell lines, the cell cycle was the same in these three cell lines. In the YCC-3C3 cell line, drug sensitivity to etoposide and cisplatin was increased when we compared it to those of the YCC-3v cell line(etoposide, 50% versus 83%; cisplatin, 67% versus 83%). However, there was no chemo-sensitization effect with vincristine, vinblastine and carboplatin. After exposure to cisplatin, a G0/G1 check-point effect was found in the YCC-3C3 cell line, but not in the YCC-3v cell line. No differences were found in telomerase activity, TRFs length or DNA fragmentation between the YCC-3v and YCC-3C3 cell lines after cisplatin treatment.
CONCLUSION
Wild-type p53 gene transduction in the gastric cancer cell line induced sensitization to the cytotoxicity of etoposide and cisplatin. This suggests the possible application of combined chemo-gene therapy with an EP regimen and wild-type p53 in gastric cancer patients with p53 mutation.

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Subtypes of Epstein - Barr Virus in Malignant Lymphoma in Korea: Kyung Eun Choi, Eun Yoon Cho, Chan Kum Park, Won Keun Lee, Young Hyeh Ko; J Korean Cancer Assoc. 1998;30(2):338-349.

Abstract PDF: PURPOSE
Epstein-Barr virus(EBV) exists in the human population in two genetic forms, usually referred to as type 1 and type 2 which have been defined on the basis of sequence divergence in the EBNA-2 and EBNA-3 family genes. In this study, we were intended to investigate whether the subtypes of EBV in malignant lymphoma in Korea were associated with specific disease entities and geographical distribution.
MATERIALS AND METHODS
Biopsy samples obtained from 18 Korean patients with malignant lymphoma including Hodgkin's disease(3 cases), B cell lymphoma(1 case), and NK/T cell lymphoma(14 cases) were analyzed to determine the subtype of EBV infected therein. DNA was extracted from formalin-fixed, paraffin-embeded tissues by ordinary method and specific viral sequences were sought using the polymerase chain reaction(PCR) and Southern blot hybridization assay. Oligonucleotide primers used for examination of EBV strain type were derived from the EBNA-3B and EBNA-3C coding regions. As a control, four cases of reactive hyperplasia were analyzed.
RESULTS
The two of four reactive hyperplasia cases were associated with type 1 and the rest of two cases with both types. Among the 18 cases with malignant lymphoma, thirteen cases(72%) had type 1, one(6%) had type 2, and four(22%) had dual infections with both types. In case of NK/T cell lymphoma(14 cases) occupying 78% of 18 biopsy samples, 86%(12 cases) were associated with type 1, 7%(1 case) with type 2, and 7%(1 case) with both types. In case of Hodgkin's disease, all of three cases had both types. B cell lymphoma taking only one case of twenty two cases was determined as type 1.
CONCLUSION
These observations indicated that type 1 EBV was predominant in Korean patients with malignant lymphoma, especially NK/T cell lymphoma and showed high frequency of dual viral infections(22%) in Hodgkin's disease as well as in reactive hyperplasia.

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Type IV Collagen and E-cadherin Expression of Progressive Uterine Cervical Epithelial Lesions: Mee Young Sol, Jee Yeon Kim; J Korean Cancer Assoc. 1997;29(4):681-689.

Abstract PDF: PURPOSE
This study was designed to evaluate the role and the value as progression markers, of type IV collagen and E-cadherin in the pathogenesis of progressive uterine cervical epithelial lesions.
MATERIALS AND METHODS
Materials examined were 4 cases of normal exocervical squamous epithelium, 9 of endocervical squamous metaplasias, 2 of mild dysplasias, 8 of moderate dysplasias, 15 of severe dysplasias, 12 of carcinoma in situ, 7 of microinvasive squamous cell carcinomas, and 4 cases of invasive squamous cell carcinomas. All of them were biopsied ones and products of conization and hysterectomy. The expression of type IV collagen and E-cadherin in uterine cervical epithelial lesions were studied by immunohistochemical method using monoclonal antibodies to type IV collagen and E-cadherin.
RESULTS
The expression of type IV collagen decreased relatively stepwise from squamous metaplasias to cervical intraepithelial neoplasias (CIN) and subsequently to invasive carcinomas. The expression of type IV collagen in normal uterine exocervical squamous epithelium was within normal range in contrast to variable expression in squamous metaplasia. There was no definite difference in expression pattern between early invasive carcinoma and advanced invasive carcinomas. Normal and squamous metaplastic epithelium of uterine cervix revealed membranous expression of E-cadherin and cervical intraepithelial lesions showed cytoplasmic expression or negative expression instead of membranous expression. There was clearcut difference in E-cadherin expression between normal or metaplastic epithelium and neoplastic lesions.
CONCLUSION
The change of type IV collagen expression could be an early marker in the progression of uterine cervical epithelial lesions from normal epithelium. And the loss of differentiaton and polarity and the deranged expression of E-cadherin are closely correlated on the basis of the result that the changed expression of E-cadherin was evident in the stage of transition from normal to neoplastic lesions.

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Clinical Characteristics of Korean Breast Cancer According to the Pathologic Type: Jong Suck Lee, You Sah Kim; J Korean Cancer Assoc. 1994;26(1):70-82.

Abstract PDF: Clinical characteristics of 411 patients with breast cancer, who were seen between March of 1983 and February of 1993 at the Keimyung University Dongsan Hospital, were analysed ac- cording to their pathological classification. Those with incomplete medical records and with in- complete follow up were not included in this study. Pathological classification was made ac- cording the final pathological report at the time of biopsy or surgery. 1) Of 411 patients, 405 were female and six were male. The most common pathological type was invasive ductal carcinoma with 298 patients(73.58%), followed by medullary carcinoma (7.16%), lobular carcinoma(4.20%), Paget's disease(4.20%), mucinous carcinoma(3.21%), intraduc- tal carcinoma(2.72%), and other rare types. 2) Average age of the patients was 46.1 years and there was no significant difference in average ages among the different pathologic types except in the patients with secretory carcinoma. 3) The average duration of symptoms of the entire patients was seven months. 4) The average size of the tumors was 4.2 cm and there was no difference in the average sizes among the histologic types. 5) The hormone receptor was positive in 95 patients(53.4%) of 178 patients tested. In patients with invasive ductal carcinoma the positivity for the hormonal receptor was 54.9%. Nine of 10 patients with lobular carcinoma was positive for hormonal receptor but all of the seven patients with medullary carcinoma was hormone receptor negative. 6) Axillary lymph nodes were involved in 66.1% of the entire patients. Positive axillary nodes were found in 71.4% of patients with invasive ductal carcinoma, 76.5% with lobular carcinoma, 64.7% with Paget's disease and 55.2% with medullary carcinoma. 7) In the six male patients, invasive ductal carcinoma was found in three patients, intraductal carcinoma in one patient, papillary carcinoma in one patient, and hemangio- pericytoma in one patient. The patient with intraductal carcinoma was 39 years old but average age of the remaining 5 patients was 54.2% years.

2,823 View
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