Cancer Research and Treatment

Original Articles

Gynecologic cancer

Frequency of Mismatch Repair Deficiency/High Microsatellite Instability and Its Role as a Predictive Biomarker of Response to Immune Checkpoint Inhibitors in Gynecologic Cancers: Joseph J. Noh, Min Kyu Kim, Min Chul Choi, Jeong-Won Lee, Hyun Park, Sang Geun Jung, Won Duk Joo, Seung Hun Song, Chan Lee; Cancer Res Treat. 2022;54(4):1200-1208. Published online December 13, 2021; DOI: https://doi.org/10.4143/crt.2021.828

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Purpose
This study was to investigate the frequency of mismatch repair deficiency/high microsatellite instability (MMRd/MSI-H) in gynecologic malignancies and the efficacy of immune checkpoint inhibitors (ICIs) in patients with recurrent gynecologic cancers according to MMR/MSI status.
Materials and Methods
We conducted a multi-center retrospective review on the patients who were diagnosed with gynecologic cancers between 2015 and 2020. Their clinicopathologic information, results of immunohistochemistry staining for MLH1/MSH2/MSH6/PMS2 and MSI analysis, tumor response to treatment with ICIs were investigated.
Results
Among 1,093 patients included in the analysis, MMRd/MSI-H was most frequent in endometrial/uterine cancers (34.8%, 164/471), followed by ovarian, tubal, and peritoneal cancers (12.8%, 54/422) and cervical cancer (11.3%, 21/186). When assessed by histology without regard for cancer types, the frequency of MMRd/MSI-H was 11.0% (38/345) in high-grade serous adenocarcinoma, 38.6% (117/303) in endometrioid adenocarcinoma, and 30.2% (16/53) in carcinosarcoma. A total of 114 patients were treated with ICIs at least once. The objective response rate (ORR) was 21.6% (8/37) in cervical cancer, 4.7% (2/43) in ovarian cancer, and 25.8% (8/31) in endometrial/uterine cancers. Univariate regression analysis identified MMRd/MSI-H as the only significant factor associated with the ORR (28.9% [11/38] vs. 11.8% [9/76]; odds ratio, 3.033; 95% confidence interval, 1.129–8.144; p=0.028).
Conclusion
The frequency of MMRd/MSI-H is moderate to high in gynecologic cancers in the Korean population. MMRd/MSI-H could be effective predictive biomarkers in gynecologic cancers of any type.

Citations

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Immunotherapy plus chemotherapy in patients with advanced endometrial cancer: a cost-effectiveness analysis
Youwen Zhu, Kun Liu, Hong Zhu
Journal of Gynecologic Oncology.2025;[Epub] CrossRef
Cervical lymphoepithelioma-like carcinoma with deficient mismatch repair and loss of SMARCA4/BRG1: a case report and five related cases
Yu Miyama, Tomomi Kato, Masayasu Sato, Akira Yabuno, Kosei Hasegawa, Masanori Yasuda
Diagnostic Pathology.2024;[Epub] CrossRef
Prognostic factors of 87 ovarian yolk sac tumor (OYST) patients and molecular characteristics of persistent and recurrent OYST
Shanhui Liang, Huijuan Ge, Shuling Zhou, Jie Tang, Yanzi Gu, Xiaohua Wu, Jin Li
Gynecologic Oncology.2024; 187: 64. CrossRef
Immunotherapy in MMR-d/MSI-H recurrent/metastatic endometrial cancer
Renata Pacholczak-Madej, Michele Bartoletti, Lucia Musacchio, Mirosława Püsküllüoglu, Paweł Blecharz, Domenica Lorusso
Expert Review of Anticancer Therapy.2024; 24(8): 717. CrossRef
Expression patterns of mismatch repair proteins in cervical cancer uncover independent prognostic value of MSH-2
Madeleine Charlotte van den Berg, Hege F Berg, Tomasz Stokowy, Erling A Hoivik, Kathrine Woie, Hilde Engerud, Akinyemi I Ojesina, Ingfrid Salvesen Haldorsen, Jone Trovik, Bjørn I Bertelsen, Camilla Krakstad, Mari Kyllesø Halle, Janie Foote
International Journal of Gynecological Cancer.2024; 34(7): 993. CrossRef
Cervical cancer: a new era
Giuseppe Caruso, Matthew K Wagar, Heng-Cheng Hsu, Jorge Hoegl, Guido Martin Rey Valzacchi, Andreina Fernandes, Giuseppe Cucinella, Seda Sahin Aker, Aarthi S Jayraj, Jessica Mauro, Rene Pareja, Pedro T Ramirez
International Journal of Gynecological Cancer.2024; 34(12): 1946. CrossRef
Unraveling the Heterogeneity of Deficiency of Mismatch Repair Proteins in Endometrial Cancer: Predictive Biomarkers and Assessment Challenges
Filomena M. Carvalho, Jesus P. Carvalho
Cancers.2024; 16(20): 3452. CrossRef
Long-term benefit of immunotherapy in a patient with squamous lung cancer exhibiting mismatch repair deficient/high microsatellite instability/high tumor mutational burden: A case report and literature review
Na Li, Zixuan Wan, Dongyan Lu, Ruilian Chen, Xiaowei Ye
Frontiers in Immunology.2023;[Epub] CrossRef
Immune escape and resistance to immunotherapy in mismatch repair deficient tumors
Guillaume Mestrallet, Matthew Brown, Cansu Cimen Bozkus, Nina Bhardwaj
Frontiers in Immunology.2023;[Epub] CrossRef
Heterogeneous expression of mismatch repair proteins and interpretation of immunohistochemical results in colorectal cancer and endometrial cancer
Xiangzhao Li, Shifen Zhang, Jiamin Zeng, Sha-sha Song, Xiaoqing Liu, Wei Kang, Minyi Liang, Rui Yang, Hong Li, Li Liang
Pathology - Research and Practice.2023; 248: 154647. CrossRef
Rechallenge with Anti-PD-1 Inhibitors in Patients with Recurrent Gynecologic Malignancies
Migang Kim, Chi-Son Chang, Min Chul Choi, Jeong-Won Lee, Hyun Park, Won Duk Joo
Yonsei Medical Journal.2023; 64(10): 587. CrossRef
Successful neoadjuvant chemotherapy plus sintilimab for locally advanced cervical cancer: case series and review of the literature
Linlin Liu, Xianbo Deng, Shuang Guo, Shouhua Yang
Diagnostic Pathology.2023;[Epub] CrossRef
Adverse Effect of the Duration of Antibiotic Use Prior to Immune Checkpoint Inhibitors on the Overall Survival of Patients with Recurrent Gynecologic Malignancies
Hye-Ji Jung, Jong-Ho Park, Jina Oh, Sae-Mi Lee, Il-Yeo Jang, Jung-Yong Hong, Yoo-Young Lee, Hyun Jin Choi
Cancers.2023; 15(24): 5745. CrossRef
Uterine carcinosarcoma with microsatellite instability - does immunotherapy modify the therapeutic scenario? A case report and literature review
Diocesio Alves Pinto Andrade, Eduardo Paulino, Isabela Panzeri Carlotti Buzatto, Danilo Tadao Wada, Warne Pedro Andrade, Andreia Cristina Melo, Angelica Nogueira-Rodrigues
Brazilian Journal of Oncology.2023;[Epub] CrossRef
Immune checkpoint inhibitors in cervical cancer: Current status and research progress
Yunkai Xie, Weimin Kong, Xiaoling Zhao, He Zhang, Dan Luo, Shuning Chen
Frontiers in Oncology.2022;[Epub] CrossRef

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Clinical Impact of Somatic Variants in Homologous Recombination Repair-Related Genes in Ovarian High-Grade Serous Carcinoma: Min Chul Choi, Sohyun Hwang, Sewha Kim, Sang Geun Jung, Hyun Park, Won Duk Joo, Seung Hun Song, Chan Lee, Tae-Heon Kim, Haeyoun Kang, Hee Jung An; Cancer Res Treat. 2020;52(2):634-644. Published online January 6, 2020; DOI: https://doi.org/10.4143/crt.2019.207

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Purpose
In this study, we investigated the frequencies of mutations in DNA damage repair genes including BRCA1, BRCA2, homologous recombination genes and TP53 gene in ovarian high-grade serous carcinoma, alongside those of germline and somatic BRCA mutations, with the aim of improving the identification of patients suitable for treatment with poly(ADP-ribose) polymerase inhibitors.
Materials and Methods
Tissue samples from 77 Korean patients with ovarian high-grade serous carcinoma were subjected to next-generation sequencing. Pathogenic alterations of 38 DNA damage repair genes and TP53 gene and their relationships with patient survival were examined. Additionally, we analyzed BRCA germline variants in blood samples from 47 of the patients for comparison.
Results
BRCA1, BRCA2, and TP53 mutations were detected in 28.6%, 5.2%, and 80.5% of the 77 patients, respectively. Alterations in RAD50, ATR, MSH6, MSH2, and FANCA were also identified. At least one mutation in a DNA damage repair gene was detected in 40.3% of patients (31/77). Germline and somatic BRCA mutations were found in 20 of 47 patients (42.6%), and four patients had only somatic mutations without germline mutations (8.5%, 4/47). Patients with DNA damage repair gene alterations with or without TP53mutation, exhibited better disease-free survival than those with TP53 mutation alone.
Conclusion
DNA damage repair genes were mutated in 40.3% of patients with high-grade serous carcinoma, with somatic BRCA mutations in the absence of germline mutation in 8.5%. Somatic variant examination, along with germline testing of DNA damage repair genes, has potential to detect additional candidates for PARP inhibitor treatment.

Citations

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Genomic instability in ovarian cancer: Through the lens of single nucleotide polymorphisms
Harshavardhani Canchi Sistla, Srikanth Talluri, Taruna Rajagopal, Sivaramakrishnan Venkatabalasubramanian, Nageswara Rao Dunna
Clinica Chimica Acta.2025; 565: 119992. CrossRef
BRCA1, BRCA2, and TP53 germline and somatic variants and clinicopathological characteristics of Brazilian patients with epithelial ovarian cancer
Caroline Stahnke Richau, Nicole de Miranda Scherer, Bruna Palma Matta, Elvismary Molina de Armas, Fábio Carvalho de Barros Moreira, Anke Bergmann, Claudia Bessa Pereira Chaves, Mariana Boroni, Anna Claudia Evangelista dos Santos, Miguel Angelo Martins Mor
Cancer Medicine.2024;[Epub] CrossRef
Proteomic landscape of epithelial ovarian cancer
Liujia Qian, Jianqing Zhu, Zhangzhi Xue, Yan Zhou, Nan Xiang, Hong Xu, Rui Sun, Wangang Gong, Xue Cai, Lu Sun, Weigang Ge, Yufeng Liu, Ying Su, Wangmin Lin, Yuecheng Zhan, Junjian Wang, Shuang Song, Xiao Yi, Maowei Ni, Yi Zhu, Yuejin Hua, Zhiguo Zheng, Ti
Nature Communications.2024;[Epub] CrossRef
T-Cell Receptor Repertoire Characteristics Associated with Prognostic Significance in High-Grade Serous Ovarian Carcinoma
Ju-Won Kim, Sewha Kim, So-Yun Yang, Je-Gun Joung, Sohyun Hwang
Genes.2023; 14(4): 785. CrossRef
Potential prognostic role of somatic mutations in a set of cancer susceptibility genes in ovarian carcinoma: A follow-up multicentric study from Pakistan
Atika Masood, Rahat Sarfaraz, Saima Zaki, Amira Shami, Saba Khaliq, Nadia Naseem
Cancer Biomarkers.2023; 36(3): 207. CrossRef
Deleterious and ethnic-related BRCA1/2 mutations in tissue and blood of Egyptian colorectal cancer patients and its correlation with human papillomavirus
Amira Salah El-Din Youssef, Abdel Rahman N. Zekri, Marwa Mohanad, Samah A. Loutfy, Nasra F. Abdel Fattah, Mostafa H. Elberry, Asmaa A. El Leithy, Ahmed El-Touny, Ahmed Samy Rabie, Mohamed Shalaby, Ayman Hanafy, Mai M. Lotfy, Enas R. El-sisi, Gharieb S. El
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Ka‐Kui Chan, Zahi Abdul‐Sater, Aditya Sheth, Dana K. Mitchell, Richa Sharma, Donna M. Edwards, Ying He, Grzegorz Nalepa, Steven D. Rhodes, D. Wade Clapp, Elizabeth A. Sierra Potchanant
Molecular Oncology.2022; 16(4): 860. CrossRef
Somatic genomic landscape of East Asian epithelial ovarian carcinoma and its clinical implications from prospective clinical sequencing: A Korean Gynecologic Oncology Group study (KGOG 3047)
Jason K. Sa, Jihye Kim, Sokbom Kang, Sang Wun Kim, Taejong Song, Seung‐Hyuk Shim, Min Chul Choi, Jae Hong No, Jae‐Yun Song, Deokhoon Kim, Yong‐Man Kim, Jae‐Hoon Kim, Jeong‐Won Lee
International Journal of Cancer.2022; 151(7): 1086. CrossRef
Analysis of Novel Variants Associated with Three Human Ovarian Cancer Cell Lines
Venugopala Reddy Mekala, Jan-Gowth Chang, Ka-Lok Ng
Current Bioinformatics.2022; 17(4): 380. CrossRef
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Alexandre André Balieiro Anastácio da Costa, Glauco Baiocchi
Seminars in Cancer Biology.2021; 77: 29. CrossRef
The Prognostic and Predictive Role of Somatic BRCA Mutations in Ovarian Cancer: Results from a Multicenter Cohort Study
Angela Toss, Claudia Piombino, Elena Tenedini, Alessandra Bologna, Elisa Gasparini, Vittoria Tarantino, Maria Elisabetta Filieri, Luca Cottafavi, Filippo Giovanardi, Stefano Madrigali, Monica Civallero, Luigi Marcheselli, Isabella Marchi, Federica Domati,
Diagnostics.2021; 11(3): 565. CrossRef
USP19 and RPL23 as Candidate Prognostic Markers for Advanced-Stage High-Grade Serous Ovarian Carcinoma
Haeyoun Kang, Min Chul Choi, Sewha Kim, Ju-Yeon Jeong, Ah-Young Kwon, Tae-Hoen Kim, Gwangil Kim, Won Duk Joo, Hyun Park, Chan Lee, Seung Hun Song, Sang Geun Jung, Sohyun Hwang, Hee Jung An
Cancers.2021; 13(16): 3976. CrossRef
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Malwina Suszynska, Piotr Kozlowski
Genes.2020; 11(7): 798. CrossRef
Prevalence of pathogenic variants in actionable genes in advanced ovarian cancer: a next-generation sequencing analysis of a nationwide registry study
Sokbom Kang, Ye L. Yu, Soo Y. Cho, Seog-Yun Park
European Journal of Cancer.2020; 141: 185. CrossRef
PARP Inhibition Increases the Reliance on ATR/CHK1 Checkpoint Signaling Leading to Synthetic Lethality—An Alternative Treatment Strategy for Epithelial Ovarian Cancer Cells Independent from HR Effectiveness
Patrycja Gralewska, Arkadiusz Gajek, Agnieszka Marczak, Michał Mikuła, Jerzy Ostrowski, Agnieszka Śliwińska, Aneta Rogalska
International Journal of Molecular Sciences.2020; 21(24): 9715. CrossRef

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Dummy Run of Quality Assurance Program before Prospective Study of Hippocampus-Sparing Whole-Brain Radiotherapy and Simultaneous Integrated Boost for Multiple Brain Metastases from Non-small Cell Lung Cancer: Korean Radiation Oncology Group (KROG) 17-06 Study: Eunah Chung, Jae Myoung Noh, Kyu Chan Lee, Jin Hee Kim, Weon Kuu Chung, Yang-Gun Suh, Jung Ae Lee, Ki Ho Seol, Hong Gyun Wu, Yeon Sil Kim, O Kyu Noh, Jae Won Park, Dong Soo Lee, Jihae Lee, Young Suk Kim, Woo-Yoon Park, Min Kyu Kang, Sunmi Jo, Yong Chan Ahn; Cancer Res Treat. 2019;51(3):1001-1010. Published online October 15, 2018; DOI: https://doi.org/10.4143/crt.2018.415

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Purpose
Lung Cancer Subcommittee of Korean Radiation Oncology Group (KROG) has recently launched a prospective clinical trial (KROG 17-06) of hippocampus-sparing whole brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in treating multiple brain metastases from non-small cell lung cancer. In order to improve trial quality, dummy run studies among the participating institutions were designed. This work reported the results of two-step dummy run procedures of the KROG 17-06 study.
Materials and Methods
Two steps tested hippocampus contouring variability and radiation therapy planning compliance. In the first step, the variation of the hippocampus delineation was investigated for two representative cases using the Dice similarity coefficients. In the second step, the participating institutions were requested to generate a HS-WBRT with SIB treatment plan for another representative case. The compliance of the treatment plans to the planning protocol was evaluated.
Results
In the first step, the median Dice similarity coefficients of the hippocampus contours for two other dummy run cases changed from 0.669 (range, 0.073 to 0.712) to 0.690 (range, 0.522 to 0.750) and from 0.291 (range, 0.219 to 0.522) to 0.412 (range, 0.264 to 0.598) after providing the hippocampus contouring feedback. In the second step, with providing additional plan priority and extended dose constraints to the target volumes and normal structures, we observed the improved compliance of the treatment plans to the planning protocol.
Conclusion
The dummy run studies demonstrated the notable inter-institutional variability in delineating the hippocampus and treatment plan generation, which could be decreased through feedback from the trial center.

Citations

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Radiotherapy trial quality assurance processes: a systematic review
Chloe Brooks, Elizabeth Miles, Peter J Hoskin
The Lancet Oncology.2024; 25(3): e104. CrossRef
Durvalumab with chemoradiotherapy for limited-stage small-cell lung cancer
Sehhoon Park, Jae Myoung Noh, Yoon-La Choi, Sang Ah Chi, Kyunga Kim, Hyun Ae Jung, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Jong-Mu Sun
European Journal of Cancer.2022; 169: 42. CrossRef
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Zoé Schmal, Claudia E. Rübe
Cancers.2022; 14(22): 5477. CrossRef
Non–coplanar whole brain radiotherapy is an effective modality for parotid sparing
Jaehyeon Park, Jae Won Park, Ji Woon Yea
Yeungnam University Journal of Medicine.2019; 36(1): 36. CrossRef

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Comparison of Ion Personal Genome Machine Platforms for the Detection of Variants in BRCA1 and BRCA2: Sang Mee Hwang, Ki Chan Lee, Min Seob Lee, Kyoung Un Park; Cancer Res Treat. 2018;50(1):255-264. Published online April 7, 2017; DOI: https://doi.org/10.4143/crt.2017.062

Abstract PDF Supplementary Material PubReader ePub

Purpose
Transition to next generation sequencing (NGS) for BRCA1/BRCA2 analysis in clinical laboratories is ongoing but different platforms and/or data analysis pipelines give different results resulting in difficulties in implementation. We have evaluated the Ion Personal Genome Machine (PGM) Platforms (Ion PGM, Ion PGM Dx, Thermo Fisher Scientific) for the analysis of BRCA1/2.
Materials and Methods
The results of Ion PGM with OTG-snpcaller, a pipeline based on Torrent mapping alignment program and Genome Analysis Toolkit, from 75 clinical samples and 14 reference DNA samples were compared with Sanger sequencing for BRCA1/BRCA2. Ten clinical samples and 14 reference DNA samples were additionally sequenced by Ion PGM Dx with Torrent Suite.
Results
Fifty types of variants including 18 pathogenic or variants of unknown significance were identified from 75 clinical samples and known variants of the reference samples were confirmed by Sanger sequencing and/or NGS. One false-negative results were present for Ion PGM/OTG-snpcaller for an indel variant misidentified as a single nucleotide variant. However, eight discordant results were present for Ion PGM Dx/Torrent Suite with both falsepositive and -negative results. A 40-bp deletion, a 4-bp deletion and a 1-bp deletion variant was not called and a false-positive deletion was identified. Four other variants were misidentified as another variant.
Conclusion
Ion PGM/OTG-snpcaller showed acceptable performance with good concordance with Sanger sequencing. However, Ion PGM Dx/Torrent Suite showed many discrepant results not suitable for use in a clinical laboratory, requiring further optimization of the data analysis for calling variants.

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Sharlize Pedroza Matute, Sasitaran Iyavoo
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Journal of Clinical Laboratory Analysis.2023;[Epub] CrossRef
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Joseph R. Habib, Yayun Zhu, Lingdi Yin, Ammar A. Javed, Ding Ding, Jonathan Tenior, Michael Wright, Syed Z. Ali, Richard A Burkhart, William Burns, Christopher L. Wolfgang, Eunji Shin, Jun Yu, Jin He
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Dose-Response Relationship between Radiation Dose and Loco-regional Control in Patients with Stage II-III Esophageal Cancer Treated with Definitive Chemoradiotherapy: Hyun Ju Kim, Yang-Gun Suh, Yong Chan Lee, Sang Kil Lee, Sung Kwan Shin, Byung Chul Cho, Chang Geol Lee; Cancer Res Treat. 2017;49(3):669-677. Published online October 6, 2016; DOI: https://doi.org/10.4143/crt.2016.354

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Purpose
The correlation between radiation dose and loco-regional control (LRC) was evaluated in patients with stage II-III esophageal cancer treated with definitive concurrent chemoradiotherapy (CRT).
Materials and Methods
Medical records of 236 stage II-III esophageal cancer patients treated with definitive CRT at Yonsei Cancer Center between 1994 and 2013were retrospectively reviewed. Among these, 120 received a radiation dose of < 60 Gy (standard-dose group), while 116 received ≥ 60 Gy (high-dose group). The median doses of radiation in the standard- and high-dose groups were 50.4 and 63 Gy, respectively. Concurrent 5-fluorouracil/cisplatin chemotherapy was administered to most patients.
Results
There were no differences in patient characteristics between the two groups except for high Karnofsky performance status and lower-thoracic lesions being more prevalent in the standard-dose group. The median progression-free survival (PFS) and overall survival (OS) times were 13.2 months and 26.2 months, respectively. Patients in the high-dose group had significantly better 2-year LRC (69.1% vs. 50.3%, p=0.002), median PFS (16.7 months vs. 11.7 months, p=0.029), and median OS (35.1 months vs. 22.3 months, p=0.043). Additionally, LRC exhibited a dose-response relationship and the complete response rate was significantly higher in the high-dose group (p=0.006). There were no significant differences in treatment-related toxicities between the groups.
Conclusion
A higher radiation dose (> 60 Gy) is associated with increased LRC, PFS, and OS in patients with stage II-III esophageal cancer treated with definitive CRT.

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He-San Luo, He-Cheng Huang, Lian-Xing Lin
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Prognostic value of tumor length and diameter for esophageal squamous cell cancer patients treated with definitive (chemo)radiotherapy: Potential indicators for nonsurgical T staging
Hongyao Xu, Shengxi Wu, Hesan Luo, Chuyun Chen, Lianxing Lin, Hecheng Huang, Renliang Xue
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Masaru Hayami, Masayuki Watanabe, Naoki Ishizuka, Shinji Mine, Yu Imamura, Akihiko Okamura, Takanori Kurogochi, Kotaro Yamashita
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Definite intensity‐modulated radiotherapy with concurrent chemotherapy more than 4 cycles improved survival for patients with locally‐advanced or inoperable esophageal squamous cell carcinoma
He‐Yuan Hsieh, Chung‐Ping Hsu, Hui‐Ling Yeh, Cheng‐Yen Chuang, Jai‐Fu Lin, Chen‐Fa Chang
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Comparison of definite chemoradiation therapy with carboplatin/paclitaxel or cisplatin/5-fluoruracil in patients with squamous cell carcinoma of the esophagus
Stefan Münch, Steffi U. Pigorsch, Michal Devečka, Hendrik Dapper, Wilko Weichert, Helmut Friess, Rickmer Braren, Stephanie E. Combs, Daniel Habermehl
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Definitive radiotherapy dose escalation with chemotherapy for treating non-metastatic oesophageal cancer
Chao-Yueh Fan, Yu-Fu Su, Wen-Yen Huang, Hsing-Lung Chao, Kuen-Tze Lin, Chun-Shu Lin
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The role of definitive chemoradiation in patients with non-metastatic oesophageal cancer
Paul M. Jeene, Hanneke W.M. van Laarhoven, Maarten C.C.M. Hulshof
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Nedaplatin‑based chemotherapy regimens combined with concurrent radiotherapy as first‑line treatment for stage II‑III esophageal squamous cell carcinoma
Huiping Zhu, Xiaolin Ge, Yufeng Lu, Yun Zuo, Qin Qin, Xinchen Sun, Min Yang
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Improved survival with higher radiation dose for esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy
Yuxia Deng, Chao Bian, Hua Tao, Haijun Zhang
Oncotarget.2017; 8(45): 79662. CrossRef

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Analysis of the Clinicopathological Characteristics of Gastric Cancer in Extremely Old Patients: Il Woong Sohn, Da Hyun Jung, Jie-Hyun Kim, Hyun Soo Chung, Jun Chul Park, Sung Kwan Shin, Sang Kil Lee, Yong Chan Lee; Cancer Res Treat. 2017;49(1):204-212. Published online June 27, 2016; DOI: https://doi.org/10.4143/crt.2016.163

Abstract PDF PubReader ePub

Purpose
Gastric cancer is the third-leading cause of cancer-related death in Korea. As the Korean population is ageing, the number of extremely old patients with this disease is increasing. This study examined the clinicopathological characteristics of gastric cancer in extremely old (over 85 years) patients who received treatment or conservative observations and compared the treatment outcomes according to the treatment modality.
Materials and Methods
A total of 170 patients over 85 years of age were diagnosed with gastric cancer. Of these, 81 underwent treatment for gastric cancer and 89 received conservative observations. The clinicopathological characteristics of the treatment and conservative groupswere compared.
Results
The mean age of the patients was 86.5 years. The conservative group included significantly more patients with older ages, macroscopically advanced cancer and upper-middle located cancer. The overall survival rate of the treatment group was significantly higher than that of the conservative group. The disease-specific mortality rate was significantly lower in the treatment group than in the conservative group. Multivariate analysis revealed the clinical course, alarm sign, and macroscopic classification to be independent prognosis factors.
Conclusion
By itself, the chronological age should not be used as a strategy to determine whether treatmentwill be administered for gastric cancer. Patientswho have early gastric cancer or lower-risk preexisting comorbidities should not be discouraged from treatment, even if they are older than 85 years.

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Yonghoon Choi, Nayoung Kim, Ki Wook Kim, Hyeong Ho Jo, Jaehyung Park, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Dong Ho Lee
Annals of Geriatric Medicine and Research.2022; 26(1): 33. CrossRef
Survival benefits of gastrectomy compared to conservative observation for older patients with resectable gastric cancer: a propensity score matched analysis
Shuhei Ito, Kippei Ohgaki, Tetsuro Kawazoe, Huanlin Wang, Toshihiko Nakamura, Shinichiro Maehara, Eisuke Adachi, Yoichi Ikeda, Yoshihiko Maehara
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C.R. Akshatha, Smitha Bhat, R. Sindhu, Dharini Shashank, Sarana Rose Sommano, Wanaporn Tapingkae, Ratchadawan Cheewangkoon, Shashanka K. Prasad
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Utility of monthly minodronate for osteoporosis after gastrectomy: Prospective multicenter randomized controlled trials
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Is surgery the best treatment for elderly gastric cancer patients?
Yoshihiko Kawaguchi, Hidenori Akaike, Katsutoshi Shoda, Shinji Furuya, Naohiro Hosomura, Hidetake Amemiya, Hiromichi Kawaida, Hiroshi Kono, Daisuke Ichikawa
World Journal of Gastrointestinal Surgery.2021; 13(11): 1351. CrossRef
The role of surgery in patients aged 85 years or older with resectable gastric cancer: a propensity score matching analysis of the SEER database
Jing Guo, Junhui Yu, Zhengshui Xu, Xuejun Sun, Jianbao Zheng
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Elderly patients with cancer admitted to intensive care unit: A multicenter study in a middle-income country
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Xuefei Wang, Junjie Zhao, Mark Fairweather, Tingsong Yang, Yihong Sun, Jiping Wang
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Lei Ding, Yuan Tian, Ling Wang, Miaomiao Bi, Dengke Teng, Sen Hong
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Age does not influence efficacy of ramucirumab in advanced gastric cancer: Subgroup analyses of REGARD and RAINBOW
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A Survey of Stereotactic Body Radiotherapy in Korea: Sun Hyun Bae, Mi-Sook Kim, Won Il Jang, Chul-Seung Kay, Woochul Kim, Eun Seog Kim, Jin Ho Kim, Jin Hee Kim, Kwang Mo Yang, Kyu Chan Lee, A Ram Chang, Sunmi Jo; Cancer Res Treat. 2015;47(3):379-386. Published online November 24, 2014; DOI: https://doi.org/10.4143/crt.2014.021

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to investigate the current status of stereotactic body radiotherapy (SBRT) in Korea. A nationwide survey was conducted by the Korean Stereotactic Radiosurgery Group of the Korean Society for Radiation Oncology (KROG 13-13).
Materials and Methods
SBRT was defined as radiotherapy with delivery of a high dose of radiation to an extracranial lesion in ≤ 4 fractions. A 16-questionnaire survey was sent by e-mail to the chief of radiation oncology at 85 institutions in June 2013.
Results
All institutions (100%) responded to this survey. Of these, 38 institutions (45%) have used SBRT and 47 institutions (55%) have not used SBRT. Regarding the treatment site, the lung (92%) and liver (76%) were the two most common sites. The most common schedules were 60 Gy/4 fractions for non-small cell lung cancer, 48 Gy/4 fractions for lung metastases, 60 Gy/3 fractions for hepatocellular carcinoma, and 45 Gy/3 fractions or 40 Gy/4 fractions for liver metastases. Four-dimensional computed tomography (CT) was the most common method for planning CT (74%). During planning CT, the most common method of immobilization was the use of an alpha cradle/vacuum-lock (42%).
Conclusion
Based on this survey, conduct of further prospective studies will be needed in order to determine the appropriate prescribed doses and to standardize the practice of SBRT.

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Hyunkyung Kim, Eunju Lee, Haeun Cho, Eunji Kim, Won Il Jang, Kwangmo Yang, Yoon-Jin Lee, Tae-Jin Kim, Mi-Sook Kim
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Patterns of quality assurance and treatment planning for stereotactic body radiation therapy in India – A survey
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Carmelo Marino, Cristina Garibaldi, Ivan Veronese, Claudia Carbonini, Serenella Russo, Michele Stasi, Pietro Mancosu
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Clinical Practice Patterns of Radiotherapy in Patients with Hepatocellular Carcinoma: A Korean Radiation Oncology Group Study (KROG 14-07)
Hyejung Cha, Hee Chul Park, Jeong Il Yu, Tae Hyun Kim, Taek-Keun Nam, Sang Min Yoon, Won Sup Yoon, Jun Won Kim, Mi Sook Kim, Hong Seok Jang, Youngmin Choi, Jin Hee Kim, Chul Seung Kay, Inkyung Jung, Jinsil Seong
Cancer Research and Treatment.2017; 49(1): 61. CrossRef
Application of stereotactic body radiation therapy to cancer liver metastasis
Si-Yuan Zhang, Guang-Ying Zhu, Gong Li, Yi-Bao Zhang, Jian-Hao Geng
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Practical patterns for stereotactic body radiotherapy to hepatocellular carcinoma in Korea: a survey of the Korean Stereotactic Radiosurgery Group
Sun Hyun Bae, Mi-Sook Kim, Won Il Jang, Chul-Seung Kay, Woochul Kim, Eun Seog Kim, Jin Ho Kim, Jin Hee Kim, Kwang Mo Yang, Kyu Chan Lee, A Ram Chang, Sunmi Jo
Japanese Journal of Clinical Oncology.2016; 46(4): 363. CrossRef
Radiotherapy in the multidisciplinary treatment of liver cancer: a survey on behalf of the Italian Association of Radiation Oncology
Francesco Dionisi, Alessia Guarneri, Veronica Dell’Acqua, Mariacristina Leonardi, Rita Niespolo, Gabriella Macchia, Tiziana Comito, Maurizio Amichetti, Pierfrancesco Franco, Savino Cilla, Luciana Caravatta, Filippo Alongi, Giovanna Mantello
La radiologia medica.2016; 121(9): 735. CrossRef

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Case Reports

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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Jeongshim Lee, Jee Hung Kim, Mitchell Liu, Andrew Bang, Robert Olson, Jee Suk Chang
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Neelesh Shrivastava, A Balasubramanian
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Zhong-Hui Li, Fang Wang, Ping Zhang, Peng Xue, Shi-Jie Zhu
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Metastatic Breast Cancer Manifesting as Alopecia: A Case Report
Sara Wilchowski
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Nan Wang, Lin Li, Youyi Xiong, Jiangrui Chi, Xinwei Liu, Chaochao Zhong, Fang Wang, Yuanting Gu
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Puzzling Papules on the neck: Cutaneous metastasis from the breast
Ajinkya Sawant, Sumit Kar, Safa Patrick, Nitin Gangane
Journal of Cancer Research and Practice.2020; 7(2): 95. CrossRef
Topical 2′-Hydroxyflavanone for Cutaneous Melanoma
Chhanda Bose, Sharda P. Singh, Henry Igid, William C. Green, Sharad S. Singhal, Jihyun Lee, Philip T. Palade, Aditya Rajan, Somedeb Ball, Vijay Tonk, Ashly Hindle, Michelle Tarbox, Sanjay Awasthi
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Exuberant case of cutaneous metastasis of breast cancer
Vítor Angelo Ferreira, Karla Spelta, Lucia Martins Diniz, Elton Almeida Lucas
Anais Brasileiros de Dermatologia.2018; 93(3): 429. CrossRef
Magnetic resonance imaging appearance of soft-tissue metastases: our experience at an orthopedic oncology center
Jennifer Sammon, Abhishek Jain, Robert Bleakney, Rakesh Mohankumar
Skeletal Radiology.2017; 46(4): 513. CrossRef

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Two Cases of Humoral Hypercalcemia of Malignancy in Metastatic Cholangiocarcinoma: Seungtaek Lim, Jungwoo Han, Kyeong Hye Park, Won Jai Jung, Yong Kang Lee, Ara Choi, Young Jae Kim, Jong-Chan Lee, Hye Jin Choi; Cancer Res Treat. 2013;45(2):145-149. Published online June 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.2.145

Abstract PDF PubReader ePub

Humoral hypercalcemia of malignancy (HHM) is rarely associated with cholangiocarcinoma (CC), and represents dismal prognosis. A 63-year-old male was admitted for evaluation of an intrahepatic mass. He was diagnosed with HHM associated with locally advanced CC. As the tumor responded to the concurrent chemoradiotherapy with capecitabine and cisplatin, serum calcium level was normalized. However, according to the disease progression, he suffered recurrence of HHM and he expired approximately one year after initial diagnosis. A 68-year-old male who presented with abdominal pain was diagnosed with metastatic CC. After the eighth cycle of gemcitabine and cisplatin, progression of the disease was found with HHM. He was treated with the best supportive care, until his demise approximately one month after the diagnosis of HHM. We report on two cases of HHM associated with CC that demonstrate strong correlation between hypercalcemia and disease burden.

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Hannah Reichert, Alexandra Macleod, Leslie Sharkey, Cornelia Peterson
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Eirini Konstantinidou, Jordan R. Maurer, Stephanie L. Reyes, Islam Baiev, Jennifer R. Stanton, Ryan D. Nipp, Lipika Goyal
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Ruben Manuel Luciano Colunga Biancatelli, Marco Ciacciarelli, Alessandro Polidoro, Piera Clemenzi, Viviana Congedo, Leonardo Calvosa, Eleonora D’Armiento, Carmen Misurale, Davide Bellini, Stefano Badia, Massimiliano Mancini, Vincenzo Petrozza, Luigi Iulia
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Humoral Hypercalcemia of Malignancy with a Parathyroid Hormone-Related Peptide-Secreting Intrahepatic Cholangiocarcinoma Accompanied by a Gastric Cancer
Katsushi Takeda, Ryosuke Kimura, Nobuhiro Nishigaki, Shinya Sato, Asami Okamoto, Kumiko Watanabe, Sachie Yasui
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Denosumab is Effective for Controlling Serum Calcium Levels in Patients with Humoral Hypercalcemia of Malignancy Syndrome: A Case Report on Parathyroid Hormone-related Protein-producing Cholangiocarcinoma
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Original Articles

A Phase II Study of Weekly Paclitaxel, Cisplatin and Concurrent Radiation Therapy for Locally-Advanced Unresectable Non-Small Cell Lung Cancer: Early Closure due to Lack of Efficacy: Se Hoon Park, Mi Kyung Kim, Sun Young Kyung, Young-Hee Lim, Chang Hyeok An, Jeong Woong Park, Seong Hwan Jeong, Jae Woong Lee, Kyu Chan Lee, Eun Kyung Cho, Soo Mee Bang, Dong Bok Shin, Jae Hoon Lee; Cancer Res Treat. 2004;36(5):293-297. Published online October 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.5.293

Abstract PDF PubReader ePub: Purpose
In this phase II study, the efficacy and safety of weekly paclitaxel concomitant with cisplatin and thoracic radiotherapy (TRT) was evaluated in patients with locally-advanced unresectable non-small cell lung cancer (NSCLC).
Materials and Methods
Patients with stage III NSCLC (without pleural effusion or cervical lymphadenopathy) received TRT (63 Gy in 35 fractions over 7 weeks) with concurrent weekly cisplatin 20 mg/m² and paclitaxel 40 mg/m²/week infused over 3 hours. In patients without evidence of disease progression, the administration of a further 2 cycles of consolidation chemotherapy, consisting of paclitaxel 175 mg/m² and cisplatin 75 mg/m², were planned after completion of the TRT.
Results
Between Feb 2000 and Dec 2002, 20 patients were entered into the study; 13 completed all 7 weeks of treatment (median 7.6 weeks; range 3.3 to 9.4). Seven out of 16 (43.8%) objective responses were observed, with 15 (75%) patients experiencing at least one episode of grade 3/4 toxicity. The main toxicities were moderate to severe neutropenia and gastrointestinal toxicity.
Conclusion
The unsatisfactory response rate and the high incidence of grade 3/4 hematologic and non-hematologic toxicities, including 7 early discontinuations of treatment and exceeding the study stopping rules, prompted the early closure of the study. In view of the activity observed, the protocol was amended to protracted continuous infusion paclitaxel, cisplatin and concurrent TRT.

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Alterations in Promoter Usage and Expression Levels of Insulin-like Growth Factor-II and H19 Genes in Cervical and Endometrial Cancer: Chan Lee, Seung Jo Kim, Joong Yol Na, Chang Suk Park, Sun Young Lee, In Ho Kim, Yu Kyoung Oh; Cancer Res Treat. 2003;35(4):314-322. Published online August 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.4.314

Abstract PDF

PURPOSE
The biallelic expression of insulin-like growth factor-II (IGF2) and H19 has been reported to be associated with the progression of several tumors. Here, the promoter usage and expression levels of IGF2 and H19 are reported to be altered in cervical and endometrial cancers showing loss of imprinting (LOI).
MATERIALS AND METHODS
The imprinting status of IGF2 and H19 was examined in 32 cervical carcinomas, their matched normal tissues, 13 endometrial cancer and 33 normal endometrial tissues.
RESULTS
The LOI of IGF2 was observed in 7 of 18 (39%) and 1 of 13 (8.3%) informative cervical carcinomas and informative endometrial cancers, respectively. The LOI of the H19 gene was detected in 5 of 14 (36%) and in all 11 (100%) informative cervical carcinoma cases and informative endometrial cancer cases, respectively. The use of promoter P1 was observed in the LOI tumors of IGF2, but not in the tumors showing maintenance of IGF2 imprinting (MOI), or in cervical and endometrial cancers. Unlike MOI tumors, some LOI tumors revealed a lack of IGF2 transcription from the promoter P3. The LOI tumors of IGF2 showed increased expression of the IGF2 level, but a down-regulation of the H19, relative to normal tissues, whereas the MOI tumors revealed no significant alterations.
CONCLUSION
These results suggest that the promoter P1 could be involved in the biallelic expression of IGF2, and that the altered expression of the IGF2 and H19 levels might be associated with the progression of cervical and endometrial cancers that exhibit biallelic IGF2 expression.

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Lei Liu, Fang Fang, Xinyi Lu
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Hui Sun, Qing Chang, Ya-Shu Liu, Yu-Ting Jiang, Ting-Ting Gong, Xiao-Xin Ma, Yu-Hong Zhao, Qi-Jun Wu
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Faiza Naz, Imran Tariq, Sajid Ali, Ahmed Somaida, Eduard Preis, Udo Bakowsky
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Deregulation of H19 is associated with cervical carcinoma
Anirban Roychowdhury, Sudip Samadder, Pijush Das, Dipanjana Indra Mazumder, Ankita Chatterjee, Sankar Addya, Ranajit Mondal, Anup Roy, Susanta Roychoudhury, Chinmay Kumar Panda
Genomics.2020; 112(1): 961. CrossRef
PIM protein kinases regulate the level of the long noncoding RNA H19 to control stem cell gene transcription and modulate tumor growth
Neha Singh, Sathish K. R. Padi, Jeremiah J. Bearss, Ritu Pandey, Koichi Okumura, Himisha Beltran, Jin H. Song, Andrew S. Kraft, Virginie Olive
Molecular Oncology.2020; 14(5): 974. CrossRef
An updated review of the H19 lncRNA in human cancer: molecular mechanism and diagnostic and therapeutic importance
Behnam Alipoor, Seyedeh Nasrin Parvar, Zolfaghar Sabati, Hamid Ghaedi, Hassan Ghasemi
Molecular Biology Reports.2020; 47(8): 6357. CrossRef
Advances of Long Noncoding RNAs-mediated Regulation in Reproduction
Kang-Sheng Liu, Tai-Ping Li, Hua Ton, Xiao-Dong Mao, Ya-Jun Chen
Chinese Medical Journal.2018; 131(2): 226. CrossRef
Dysregulated expression of long noncoding RNAs in gynecologic cancers
Elahe Seyed Hosseini, Matthieu Meryet-Figuiere, Hamed Sabzalipoor, Hamed Haddad Kashani, Hossein Nikzad, Zatollah Asemi
Molecular Cancer.2017;[Epub] CrossRef

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Screening and Cloning of Genes Preferentially Expressed in Aminopterin-Treated Myeloma Cell Apoptosis: Hong Chan Lee, Sung Joo Kim, Sarah Yoon, Sung Joon Kwon, Yong Hoon Chung; J Korean Cancer Assoc. 2000;32(3):655-664.

Abstract: PURPOSE
When murine myeloma cells P3-X63-Ag8.653 (V653) of this model treated with amin opterin, an anticancer drug, they can't synthesize nucleic acid via de novo or salvage pathway and selectively eliminated due to apoptosis. This study was aimed to clone specific known and novel genes preferentially expressed in aminopteirn-treated tumor cell apoptosis.
MATERIALS AND METHODS
This study was aimed to clone specific known and novel genes pre ferentially expressed in aminopteirn-treated tumor cell apoptosis by using subtraction-PCR technique.
RESULTS
By using this technique 868 clones were obtained. Of these 427 clones were positive with insert DNA. By using cross-hybridization Southern blotting, final 101 clones were selected. All of these genes were sequenced and analyzed by using genebank DNA database. Total 101 clones of genes preferentially expressed in apoptotic tumor cells were classified into 10 groups, which included ribosomal proteins, nuclear proteins, mitdegrees Chondrial proteins, signal transductional proteins, retroviral proteins, cell surface receptor proteins, cell structural proteins, unclassified miscellaneous proteins, and novel genes. Especially, Unknown novel genes preferentially ex pressed in this apoptotic tumor cells included clone numbers S1-63, 1-1, 1-3, 1-16, 1-18, 1-20, 3-33, 3-41, 3-44, 3-48, 3-55, 3-60, 6-17, 6-25, 8-12, 50-7, 50-23, and 100-35.
CONCLUSION
It seemed that known and unknown novel genes cloned in this study would con tribute to the future studies regarding apoptosis of tumor cells and cancer treatment therepy.

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The Breast Cancer in Women Less Than 36 Years of Age: Byung Chan Lee, Se Joong Kim, Woo Jung Lee, Duk Joo Moon, Kyung Shik Lee; J Korean Cancer Assoc. 1999;31(2):289-296.

Abstract PDF: PURPOSE
There is still much controversy about the prognosis of breast cancer developed in young women compared with old women. We performed this study to evaluate the pragnosis of the breast cancer in young women.
MATERIALS AND METHODS
From 1985 to 1994, 1189 women received opetaticms for breast cancers at Severance Hospital. The study group included patients less than 36 years old who had unilateral, invasive and primary operable breast eancers (N=158). The control groups included patients between 36 and 50 years old (N=518) and those between 51 and 65 years old (N=269) who had the same conditions as the study group. The 5-year survival and 5-year disease-free survival rate for three groups were compared using Kaplan-Meier method and Log-rank method. To evaluate the age as an independent prognostic factor in premenopausal women Coxs proportional hazard model was used.
RESULT
The overall 5-year survival rate and 5-year disease-free survival rate ot the study group were significantly lower than those of control groups (p<0.05). There was no significant difference in 5-year survival and S-year disease free survival between the two control groups. The Coxs propotional hazard model analysis revealed that the stage is the most important prognostic factor and the age was also an independent prognostic factor.
CONCLUSION
The prognosis of breast cancer less than 36 year old was poorer than that of 36-51 year old and 51-65 year old, suggesting that the age may be an independent prognostic factor in premenopausal women. More aggessive adjuvant treatment is required for breast cancer patients less than 36 year old of age.

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Mucinous Carcinoma of the Breast: Seung Sang Ko, Byung Chan Lee, Kyung Shik Lee; J Korean Cancer Assoc. 1999;31(1):98-104.

Abstract PDF: PURPOSE
Mucinous carcinoma of the breast is relatively rare among the malignant breast lesions. It has distinctive pathological and behavioral characteristics to separate from other types of breast cancers. Accoding to the WHO definition, mucinous carcinoma of the breast is a carcinoma containing large amounts of extracellular epithelial mucus, sufficient to be visible grossly, and recognizable microscopically surrounding and within tumor cells. Mucinous carcinoma shows the characteristic features clinically and histologically because of the mucus production by the tumor.
MATERIALS AND METHODS
We reviewed 29 cases of mucinous carcinoma that had been treated from 1985 to 1996 in the Department of General Surgery, Yonsei University College of Medicine.
RESULTS
The results were as follows: The prevalent age group was the fifth decade (37.9%). The 27 cases were female and 2 were male. The most common sign and symptom was a palpable mass (100%). The most patients visited the hospital within 2 months of onset (55.2%). Most frequent tumor size was 2-3 cm in diameter, found in 10 cases (34.5%), and 13.8% of cases was more than 5 cm in diameter. The most frequent site of tumor was the upper outer quadrant in 16 cases (55.2%). The operations performed were as follows: Modified radical mastectomy (Auchincloss or Patey) in 24 cases (82.8%), quadrantectomy with axillary lymph node dissection in 4 cases (13.8%), simple mastectomy with lower axillar dissection in 1 cases (3.4%). Axillary lymph node metastasis was present in 3 cases (10.3%). The most common stage at diagnosis was stage IIa in 13 cases (44.8%).
CONCLUSION
This study shows some characteristics of mucinous carcinoma of breast distinict from those previously proposed Further studies are needed to identify clinical parameters which characterize mucinous carcinoma of the breast.

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Increment of Telomerase Activity with Breast Cancer Progression: Kyu Hyun Park, Sun Young Rha, Tae Soo Kim, Byung Chan Lee, Sei Ho Park, Hyun Cheol Chung, Won Young Lee, Joo Hang Kim, Jae Kyung Roh, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(6):1032-1040.

Abstract PDF: PURPOSE
We studied the telomerase activity in normal and cancer tissues of the breast and then compared it to the clinical parameters.
MATERIALS AND METHODS
36 paired normal and cancerous breast tissues were assayed for telomerase activity by PCR-based TRAP assay (telomeric repeat amplification protocol). In 17 cancer tissues, flow cytometric analysis for S-phase fraction was done.
RESULTS
None of the normal breast tissue expressed telomerase activity while 23 out of 26 breast cancer tissue expressed telomerase activity (92%). Clinical parameters such as T-factor, tumor grade, hormone receptor expression, mitosis, S-phase fraction did not correlate with telomerase expression. However, telomerase acitvity increased with cancer progression such as; in a state of lymph node metastasis and in an advanced pathological stage.
CONCLUSION
Telomerase activity was expressed only from cancer tissues. And this expression increased with cancer progression suggesting a possible therapeutic target in breast cancer.

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Correlation of Tumor DNA Ploidy , Axillary Lymph Node Changes with Other Prognostic Factors in Breast Cancer: Hong Chan Lee, Pah Jong Jung, Young Hyeh Ko; J Korean Cancer Assoc. 1995;27(1):52-61.

Abstract PDF: Flow cytometric DNA analysis has been applied as an important factor for decision of postoperative therapeutic regimen and prediction of prognosis of breast cancer. Sinus histiocytosis had been recognized as a better prognosic factor in axillary lymph nodes than negative sinus histiocytosis. It represents not only the presence of metastases, but also their immunologic potential and cell mediated immunity against the tumor. This study examined DNA ploidy pattern, S-phase fraction and sinus histiocytosis in axillary lymph nodes of breast cancer in 131 patients who underwent operation at the Department of Surgery, Hanyang University Hospital during the period of January 1990 through February 1993. On the basis of these datas, we analysed the correlation of tumor DNA ploidy and axillary lymph node changes with other prognostic factors which are TNM status, histologic grade and estrogen receptor in breast cancer. Authors obtained the following results; 1) In 131 patients, aneuploidy was 63(48.1%) and high S-phase fraction was 89(68%) 2) Incidence of aneuploidy and high S-phase fraction was increased according to the aggravation of T factor, N factor and poor histiologic grade. The rate of negative estrogen receptor was high in aneuploidy and high S-phase fraction group. 3) Among 102 patients, 53(50.1%) had positive sinus histiocytosis, 49(49.9%) had negative sinus histiocytosis. The positive rate of sinus histiocytosis in axillary lymph nodes was highly related with negative axillary lymph node metastases and small size of tumor and it was lower in aneuploidy and high S-phase fraction. 4) Among the patients as a whole postoperative early recurrence were present in 8 cases, they had poor TNM staging and high correlation to aneuploidy, high S-phase fraction and sinus histiocytosis seem to be useful prognostic factors. And additional follow up studies for survival is required.

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The Expression of the Mutant p53 Protein in Colorectal Tumors: Seung Ik Jang, Chang Soo Kim, Jong Chan Lee, Suk Kyun Chang; J Korean Cancer Assoc. 1996;28(2):215-225.

Abstract PDF: It is known that the development of colorectal tumor needs several sequential abnormality of chromosome in 5p, I8q and 17p and chromosomal abnormality in 17p especially causes malignant transformation of colorectal tumor. The mutation of p53 gene in chromosome 17p proceed the loss of that. Abnormal nuclear protein known as mutant p53 protein is expressed in the early phase of malignant transformation of colorectal tumor. We examined the mutant p53 protein in 115 paraffin-embedded colorectal tumors and normal tissues(group 1: 15 normal tissues, group 2; 30 adenomas and group 3; 70 adenocarcinoma) by immunohistochemical method using monoclonal antibody to the mutant p53 protein. The degree of positive expression of the mutant p53 protein in each group was graded and it was compared in accordance with several prognostic factors of colorectal cancer. In normal tissues and adenomas, positive expression of the mutant p53 protein was not found. In adenocarcinoma, the mutant p53 protein was positively expressed with gradual decreasing tendency from 50.0% of Dukes' A, 48.0% of Dukes' B, 40.9% of Dukes' C to 26.7 % of Dukes' D. The positivity of Dukes' A, B, and C was significantly different from that of Dukes' D.(p<0.05). The mutant p53 protein in adenocarcinoma without lymph nodes involvement, lymphatic invasion, perineural invasion and vein invasion was positively expressed as 48.5%, 47.8%, 50.0% and 44.1%, respectively. That was expressed higher than 39.4% , 38.3%, 20.0% and 27.3% in same group with positive pathologic findings(p<0.05, *p<0.01). The mutant p53 protein in adenocarcinomas of rectum and ascending colon was positively expressed by 48.7% and 40.0%. That was expressed higher than 33.3% and 22.2% in same group of sigmoid colon and transverse and descending colon. The mutant p53 protein was positiveiy expressed in well and morderately differentiated adenocarcinoma as 45.5% and 45.3%. None of poorly differentiated adenocarcinomas and mucinous carcinomas positively expressed, From the above experiment, we found that the mutant p53 protein was exclusively expressed in adenocarcinoma and that positive expression rate was reversely correlated to the clinical staging and severity of invasiveness. In conclusion, we thought that the expression of the mutant p53 protein might have a prognostic value in the colorectal cancer.

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