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Breast cancer
A Nationwide Study on HER2-Low Breast Cancer in South Korea: Its Incidence of 2022 Real World Data and the Importance of Immunohistochemical Staining Protocols
Min Chong Kim, Eun Yoon Cho, So Yeon Park, Hee Jin Lee, Ji Shin Lee, Jee Yeon Kim, Ho-chang Lee, Jin Ye Yoo, Hee Sung Kim, Bomi Kim, Wan Seop Kim, Nari Shin, Young Hee Maeng, Hun Soo Kim, Sun Young Kwon, Chungyeul Kim, Sun-Young Jun, Gui Young Kwon, Hye Jeong Choi, So Mang Lee, Ji Eun Choi, Ae Ri An, Hyun Joo Choi, EunKyung Kim, Ahrong Kim, Ji-Young Kim, Jeong Yun Shim, Gyungyub Gong, Young Kyung Bae
Cancer Res Treat. 2024;56(4):1096-1104.   Published online March 6, 2024
DOI: https://doi.org/10.4143/crt.2024.092
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Notable effectiveness of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer (BC) has focused pathologists’ attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results.
Materials and Methods
The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected.
Results
Total 11,416 patients from 25 institutions included in this study. Of these patients, 40.7% (range, 6.0% to 76.3%) were classified as HER2-zero, 41.7% (range, 10.5% to 69.1%) as HER2-low, and 17.5% (range, 6.7% to 34.0%) as HER2-positive. HER2-low tumors were associated with positive estrogen receptor and progesterone receptor statuses (p < 0.001 and p < 0.001, respectively). Antigen retrieval times (≥ 36 minutes vs. < 36 minutes) and antibody incubation times (≥ 12 minutes vs. < 12 minutes) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3,259) of the patients.
Conclusion
The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

Citations

Citations to this article as recorded by  
  • Impact of immunohistochemistry staining conditions on the incidence of human epidermal growth factor receptor 2 (HER2)-low breast cancer
    Min Chong Kim, Sun Young Kwon, Hye Ra Jung, Young Kyung Bae
    Virchows Archiv.2024; 485(6): 1117.     CrossRef
  • Breast Cancer: Extracellular Matrix and Microbiome Interactions
    Lourdes Herrera-Quintana, Héctor Vázquez-Lorente, Julio Plaza-Diaz
    International Journal of Molecular Sciences.2024; 25(13): 7226.     CrossRef
  • 3,275 View
  • 219 Download
  • 2 Web of Science
  • 2 Crossref
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Genitourinary cancer
Clinical Outcomes of Small Cell Carcinoma of the Genitourinary Tract and the Prognostic Significance of the Tumor Immune Microenvironment
Jaewon Hyung, Hyung-Don Kim, Gi Hwan Kim, Yong Mee Cho, Yeon-Mi Ryu, Sang-Yeob Kim, Inkeun Park, Shinkyo Yoon, Jae Lyun Lee
Cancer Res Treat. 2024;56(2):624-633.   Published online November 29, 2023
DOI: https://doi.org/10.4143/crt.2023.1076
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Small cell carcinoma of the genitourinary tract (GU SCC) is a rare disease with a poor prognosis. There are only limited treatment options due to insufficient understanding of the disease. In this study, we analyzed the clinical outcomes of patients with GU SCC and their association with the tumor immune phenotype.
Materials and Methods
Patients diagnosed with GU SCC were included. Survival outcomes according to the primary location (prostate and non-prostate) and stages (limited disease [LD] and extensive disease [ED]) were analyzed. We performed multiplex immunohistochemistry (IHC) in non-prostate SCC patients and analyzed the immune cell population.
Results
A total of 77 patients were included in this study. Their median age was 71 years, 67 patients (87.0%) were male, and 48 patients (62.3%) had non-prostate SCC. All patients with ED (n=31, 40.3%) received etoposide plus platinum (EP) as initial treatment and median overall survival (OS) was 9.7 months (95% confidence interval [CI], 7.1 to 18.6). Patients with LD (n=46, 59.7%) received EP followed by radiotherapy or surgery, and 24-months OS rate was 63.6% (95% CI, 49.9 to 81.0). The multiplex IHC analysis of 21 patients with non-prostate SCC showed that patients with a higher density of programmed death-ligand 1–expressing CD68+CD206+ M2-like macrophages had significantly worse OS outcomes with an adjusted hazards ratio of 4.17 (95% CI, 1.25 to 14.29; adjusted p=0.02).
Conclusion
Patients with GU SCC had a poor prognosis, even those with localized disease. The tumor immune phenotypes were significantly associated with survival. This finding provides new insights for treating GU SCC.
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Genitourinary Cancer
Ferroportin and FBXL5 as Prognostic Markers in Advanced Stage Clear Cell Renal Cell Carcinoma
Cheol Keun Park, Jayoon Heo, Won Sik Ham, Young-Deuk Choi, Sang Joon Shin, Nam Hoon Cho
Cancer Res Treat. 2021;53(4):1174-1183.   Published online March 17, 2021
DOI: https://doi.org/10.4143/crt.2021.031
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Advanced stage clear cell renal cell carcinoma (ccRCC) involves a poor prognosis. Several studies have reported that dysfunctions in iron metabolism‒related proteins may cause tumor progression and metastasis of this carcinoma. In this study, we investigated the impact of the expression of iron metabolism‒related proteins on patient prognoses in advanced stage ccRCCs.
Materials and Methods
All of 143 advanced stage ccRCC specimens were selected following validation with double blind reviews. Several clinicopathological parameters including nuclear grade, perirenal fat invasion, renal sinus fat invasion, vascular invasion, necrosis, and sarcomatoid/rhabdoid differentiation were compared with the expression of ferroportin (FPN), and F-Box and leucine rich repeat protein 5 (FBXL5), by immunohistochemistry. FPN and FBXL5 mRNA level of ccRCC from The Cancer Genome Atlas database were also analyzed for validation.
Results
FPN and FBXL5 immunohistochemistry showed membrane and cytoplasmic expression, respectively. Based on the H-score, cases were classified as low or high expression with a cutoff value of 20 for FPN and 15 for FBXL5, respectively. Low expression of FPN and FBXL5 were significantly associated with patient death (p=0.022 and p=0.005, respectively). In survival analyses, low expression of FPN and FBXL5 were significantly associated with shorter overall survival (p=0.003 and p=0.004, respectively). On multivariate analysis, low expression of FBXL5 (hazard ratio, 2.001; p=0.034) was significantly associated with shorter overall survival.
Conclusion
FPN and FBXL5 can be used as potential prognostic markers and therapeutic targets for advanced stage ccRCC.

Citations

Citations to this article as recorded by  
  • Differences in genomic profile of high-grade urothelial carcinoma according to tumor location
    Cheol Keun Park, Nam Hoon Cho
    Urologic Oncology: Seminars and Original Investigations.2022; 40(3): 109.e1.     CrossRef
  • The Role of Iron in Cancer Progression
    Qianqian Guo, Liwen Li, Shanshan Hou, Ziqiao Yuan, Chenhui Li, Wenzhou Zhang, Lufeng Zheng, Xiaoman Li
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • 6,351 View
  • 140 Download
  • 3 Web of Science
  • 2 Crossref
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Gastrointestinal cancer
Spatial Distribution and Prognostic Implications of Tumor-Infiltrating FoxP3- CD4+ T Cells in Biliary Tract Cancer
Hyung-Don Kim, Jwa Hoon Kim, Yeon-Mi Ryu, Danbee Kim, Sunmin Lee, Jaehoon Shin, Seung-Mo Hong, Ki-Hun Kim, Dong‐Hwan Jung, Gi‐Won Song, Dae Wook Hwang, Jae Hoon Lee, Ki Byung Song, Baek-Yeol Ryoo, Jae Ho Jeong, Kyu-pyo Kim, Sang-Yeob Kim, Changhoon Yoo
Cancer Res Treat. 2021;53(1):162-171.   Published online August 31, 2020
DOI: https://doi.org/10.4143/crt.2020.704
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated.
Materials and Methods
A total of 52 BTC patients treated with palliative gemcitabine plus cisplatin were included. Multiplexed immunohistochemistry was performed on tumor tissues, and immune infiltrates were separately analyzed for the stroma, tumor margin, and tumor core.
Results
The density of CD8+ T cells, FoxP3- CD4+ helper T cells, and FoxP3+ CD4+ regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. The density of LAG3- or TIM3-expressing CD8+ T cell and FoxP3- CD4+ helper T cell infiltrates was also higher in the tumor margin. In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. A high density of FoxP3- CD4+ helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p=0.092) and significantly better overall survival (OS) (p=0.012). In multivariate analyses, a high density of FoxP3- CD4+ helper T cells in the tumor margin was independently associated with favorable PFS and OS.
Conclusion
The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. The density of tumor margin-infiltrating FoxP3- CD4+ helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin.

Citations

Citations to this article as recorded by  
  • Infiltrating T lymphocytes and tumor microenvironment within cholangiocarcinoma: immune heterogeneity, intercellular communication, immune checkpoints
    Yunyan Dai, Chenyang Dong, Zhiming Wang, Yunpeng Zhou, Yi Wang, Yi Hao, Pinggui Chen, Chaojie Liang, Gaopeng Li
    Frontiers in Immunology.2025;[Epub]     CrossRef
  • Advancing biliary tract malignancy treatment: emerging frontiers in cell-based therapies
    Jianyang Ao, Mingtai Hu, Jinghan Wang, Xiaoqing Jiang
    Frontiers in Immunology.2025;[Epub]     CrossRef
  • Research progress of T cells in cholangiocarcinoma
    Zhiming Wang, Yunyan Dai, Yunpeng Zhou, Yi Wang, Pinggui Chen, Yaoxuan Li, Yunfei Zhang, Xiaocui Wang, Ying Hu, Haonan Li, Gaopeng Li, Yukai Jing
    Frontiers in Immunology.2025;[Epub]     CrossRef
  • Mapping of the T-cell Landscape of Biliary Tract Cancer Unravels Anatomic Subtype-Specific Heterogeneity
    Jianhua Nie, Shuyuan Zhang, Ying Guo, Caiqi Liu, Jiaqi Shi, Haotian Wu, Ruisi Na, Yingjian Liang, Shan Yu, Fei Quan, Kun Liu, Mingwei Li, Meng Zhou, Ying Zhao, Xuehan Li, Shengnan Luo, Qian Zhang, Guangyu Wang, Yanqiao Zhang, Yuanfei Yao, Yun Xiao, Sheng
    Cancer Research.2025; 85(4): 704.     CrossRef
  • Deciphering the tumor immune microenvironment from a multidimensional omics perspective: insight into next-generation CAR-T cell immunotherapy and beyond
    Zhaokai Zhou, Jiahui Wang, Jiaojiao Wang, Shuai Yang, Ruizhi Wang, Ge Zhang, Zhengrui Li, Run Shi, Zhan Wang, Qiong Lu
    Molecular Cancer.2024;[Epub]     CrossRef
  • Tumor-infiltrating T lymphocytes: A promising immunotherapeutic target for preventing immune escape in cholangiocarcinoma
    Sijia Hua, Xinyi Gu, Hangbin Jin, Xiaofeng Zhang, Qiang Liu, Jianfeng Yang
    Biomedicine & Pharmacotherapy.2024; 177: 117080.     CrossRef
  • Focusing on the Immune Cells: Recent Advances in Immunotherapy for Biliary Tract Cancer
    Luohang Ni, Jianing Xu, Quanpeng Li, Xianxiu Ge, Fei Wang, Xueting Deng, Lin Miao
    Cancer Management and Research.2024; Volume 16: 941.     CrossRef
  • Artificial Intelligence-Powered Spatial Analysis of Tumor-Infiltrating Lymphocytes as a Potential Biomarker for Immune Checkpoint Inhibitors in Patients with Biliary Tract Cancer
    Yeong Hak Bang, Choong-kun Lee, Kyunghye Bang, Hyung-Don Kim, Kyu-pyo Kim, Jae Ho Jeong, Inkeun Park, Baek-Yeol Ryoo, Dong Ki Lee, Hye Jin Choi, Taek Chung, Seung Hyuck Jeon, Eui-Cheol Shin, Chiyoon Oum, Seulki Kim, Yoojoo Lim, Gahee Park, Chang Ho Ahn, T
    Clinical Cancer Research.2024; 30(20): 4635.     CrossRef
  • Prognostic value of tumor-infiltrating lymphocytes in distal extrahepatic bile duct carcinoma
    S.-Y. Jun, S. An, S.-M. Hong, J.-Y. Kim, K.-P. Kim
    ESMO Open.2024; 9(11): 103969.     CrossRef
  • Modulation of FOXP3 Gene Expression in OVCAR3 Cells Following Rosmarinic Acid and Doxorubicin Exposure
    Veysel Toprak, İlhan Özdemir, Şamil Öztürk, Orhan Yanar, Yusuf Ziya Kizildemir, Mehmet Cudi Tuncer
    Pharmaceuticals.2024; 17(12): 1606.     CrossRef
  • The Immunomodulatory Role of Vitamin D in Regulating the Th17/Treg Balance and Epithelial–Mesenchymal Transition: A Hypothesis for Gallbladder Cancer
    Ricardo Cartes-Velásquez, Agustín Vera, Rodrigo Torres-Quevedo, Jorge Medrano-Díaz, Andy Pérez, Camila Muñoz, Hernán Carrillo-Bestagno, Estefanía Nova-Lamperti
    Nutrients.2024; 16(23): 4134.     CrossRef
  • Tumor immune microenvironment and the current immunotherapy of cholangiocarcinoma (Review)
    Siqi Yang, Ruiqi Zou, Yushi Dai, Yafei Hu, Fuyu Li, Haijie Hu
    International Journal of Oncology.2023;[Epub]     CrossRef
  • Therapeutic significance of tumor microenvironment in cholangiocarcinoma: focus on tumor-infiltrating T lymphocytes
    Chaoqun Li, Lei Bie, Muhua Chen, Jieer Ying
    Exploration of Targeted Anti-tumor Therapy.2023; 4(6): 1310.     CrossRef
  • Dynamic increase of M2 macrophages is associated with disease progression of colorectal cancers following cetuximab-based treatment
    Hyung-Don Kim, Sun Young Kim, Jihun Kim, Jeong Eun Kim, Yong Sang Hong, Buhm Han, Eunyoung Tak, Yeon-Mi Ryu, Sang-Yeob Kim, Tae Won Kim
    Scientific Reports.2022;[Epub]     CrossRef
  • Up-to-Date Pathologic Classification and Molecular Characteristics of Intrahepatic Cholangiocarcinoma
    Taek Chung, Young Nyun Park
    Frontiers in Medicine.2022;[Epub]     CrossRef
  • The role of tumor-infiltrating lymphocytes in cholangiocarcinoma
    Dong Liu, Lara Rosaline Heij, Zoltan Czigany, Edgar Dahl, Sven Arke Lang, Tom Florian Ulmer, Tom Luedde, Ulf Peter Neumann, Jan Bednarsch
    Journal of Experimental & Clinical Cancer Research.2022;[Epub]     CrossRef
  • Clinical implications of the tumor microenvironment using multiplexed immunohistochemistry in patients with advanced or metastatic renal cell carcinoma treated with nivolumab plus ipilimumab
    Jwa Hoon Kim, Gi Hwan Kim, Yeon-Mi Ryu, Sang-Yeob Kim, Hyung-Don Kim, Shin Kyo Yoon, Yong Mee Cho, Jae Lyun Lee
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response
    Tong Fu, Lei-Jie Dai, Song-Yang Wu, Yi Xiao, Ding Ma, Yi-Zhou Jiang, Zhi-Ming Shao
    Journal of Hematology & Oncology.2021;[Epub]     CrossRef
  • 8,401 View
  • 236 Download
  • 19 Web of Science
  • 18 Crossref
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PD-L1 Testing in Gastric Cancer by the Combined Positive Score of the 22C3 PharmDx and SP263 Assay with Clinically Relevant Cut-offs
Yujun Park, Jiwon Koh, Hee Young Na, Yoonjin Kwak, Keun-Wook Lee, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Hye Seung Lee
Cancer Res Treat. 2020;52(3):661-670.   Published online January 10, 2020
DOI: https://doi.org/10.4143/crt.2019.718
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We provide a comparison between 22C3 pharmDx and SP263 assay, for evaluating programmed death ligand 1 (PD-L1) expression in advanced gastric cancer (GC) patients.
Materials and Methods
The PD-L1 immunohistochemistry by 22C3 pharmDx and SP263 assays was performed in the center of the tumor (CT) and invasive margin (IM) in 379 GC tissues using tissue microarrays and interpreted as combined positive score (CPS) and tumor proportion score (TPS). Of the total samples, 55 samples were independently reviewed by five pathologists.
Results
The two assays showed a high correlation in both the CPS and TPS. At a CPS ≥ 1 cut-off, 219 (57.8%) and 231 (60.9%) GCs were positive for PD-L1 with the 22C3 and SP263 assays, and at ≥ 10 cut-off, 37 (9.8%) and 36 (9.5%) GCs were positive, respectively. The overall percent agreement (OPA) was greater than 90% with CPS ≥ 1 and ≥ 10 cut-offs, and TPS ≥ 1% and ≥ 10% cut-offs. There was higher OPA between the two assays with a CPS cut-off ≥ 10 (99.2%) than ≥ 1 (94.7%). The percent agreement between the CT and IM was higher with a CPS cut-off ≥ 10 (92.9%) than ≥ 1 (77.6%). Patient with positive expression at CPS ≥ 5 cut-off had a significantly better outcomes in both assays. Interobserver variability among five pathologists was higher than the assay variability.
Conclusion
Two assays for PD-L1 expression in GC showed high agreement. These results provide guidance for selecting eligible patients with GC for pembrolizumab treatment.

Citations

Citations to this article as recorded by  
  • PD-L1 as a Biomarker in Gastric Cancer Immunotherapy
    Yunjoo Cho, Soomin Ahn, Kyoung-Mee Kim
    Journal of Gastric Cancer.2025; 25(1): 177.     CrossRef
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    European Radiology.2025;[Epub]     CrossRef
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    Clinical and Translational Oncology.2025;[Epub]     CrossRef
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    Yusuke Miyajima, Takeshi Kawakami
    Cancers.2025; 17(7): 1120.     CrossRef
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    Choong-kun Lee, Sejung Park, Yaeji Lee, Choa Yun, Moonki Hong, Chung Mo Nam, Hyun Cheol Chung, Sun Young Rha
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    Mojun Zhu, Harry H. Yoon
    Journal of Clinical Oncology.2024; 42(4): 373.     CrossRef
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    Dordi Lea, Claudia Zaharia, Kjetil Søreide
    Cancer Treatment and Research Communications.2024; 38: 100788.     CrossRef
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    Jeffry Beta Tenggara, Andhika Rachman, Joedo Prihartono, Lisnawati Rachmadi, Sonar Soni Panigoro, Didik Setyo Heriyanto, Noorwati Sutandyo, Intan Russianna Nasution, Familia Bella Rahadiati, Ricci Steven, Rachelle Betsy, Samuel Juanputra, Aru Wisaksono Su
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    Suhaib Khateeb, Ludimila Cavalcante, Noor Alnairat, Meghana Singh, Ibrahim Halil Sahin, Azhar Saeed, Anwaar Saeed
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    V. Massa, F. Signorini, F. Salani, M.E. Filice, G. Grelli, P. Lippolis, P. Faviana, V. Genovesi, S. Santi, C. Vivaldi, S. Cesario, A. Bertolucci, C. Cremolini, V. Nardini, G. Masi, C. Ugolini, L. Fornaro
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  • A Phase 1a/1b Dose Escalation/Expansion Study of the Anti-PD-1 Monoclonal Antibody Nofazinlimab in Chinese Patients with Solid Tumors or Lymphoma
    Jifang Gong, Ye Guo, Yanqiao Zhang, Yi Ba, Tong Chen, Wei Li, Caicun Zhou, Mengzhao Wang, Haiyan Yang, Yuhong Zhou, Qiqing Cai, Ziping Wang, Gang Huang, Wei Zhang, Rila Su, Zhongheng Cai, Zenglian Yue, Jinzhou Dou, Peiqi Li, Rachel Wu, Archie N. Tse, Lin
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  • Immune checkpoint inhibitors in advanced gastroesophageal adenocarcinoma: a series of patient-level meta-analyses in different programmed death-ligand 1 subgroups
    A.G. Leone, A.S. Mai, K.Y. Fong, D.W.T. Yap, K. Kato, E. Smyth, M. Moehler, J.T.C. Seong, R. Sundar, J.J. Zhao, F. Pietrantonio
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  • HIPEC for Metastatic Gastric Cancer: Moving the Needle Towards 3-Year Survival
    Neal Bhutiani, Y. David Seo, Kristen A. Robinson, Michael G. White, Naruhiko Ikoma, Paul F. Mansfield, Jenny J. Li, Mariela Blum Murphy, Jaffer A. Ajani, Brian D. Badgwell
    European Journal of Surgical Oncology.2024; : 108790.     CrossRef
  • Biomarkers for Predicting Response to Personalized Immunotherapy in Gastric Cancer
    Moonsik Kim, Ji Yun Jeong, An Na Seo
    Diagnostics.2023; 13(17): 2782.     CrossRef
  • Development of an automated combined positive score prediction pipeline using artificial intelligence on multiplexed immunofluorescence images
    Abhishek Vahadane, Shreya Sharma, Devraj Mandal, Madan Dabbeeru, Josephine Jakthong, Miguel Garcia-Guzman, Shantanu Majumdar, Chung-Wein Lee
    Computers in Biology and Medicine.2023; 152: 106337.     CrossRef
  • CT-based delta radiomics in predicting the prognosis of stage IV gastric cancer to immune checkpoint inhibitors
    Jiazheng Li, Zifan Chen, Yang Chen, Jie Zhao, Meng He, Xiaoting Li, Li Zhang, Bin Dong, Xiaotian Zhang, Lei Tang, Lin Shen
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • Efficacy of PD-1/PD-L1 inhibitors in gastric or gastro-oesophageal junction cancer based on clinical characteristics: a meta-analysis
    Gengwei Huo, Wenjie Liu, Peng Chen
    BMC Cancer.2023;[Epub]     CrossRef
  • Clinical relevance of PD-1 positive CD8 T-cells in gastric cancer
    Joan Choo, Ley Fang Kua, Mu Yar Soe, Bernadette Reyna Asuncion, Benjamin Kye Jyn Tan, Chong Boon Teo, Ryan Yong Kiat Tay, Jimmy So, Asim Shabbir, Kim Guowei, Hon Lyn Tan, Gloria Chan, Haoran Ma, Gokula Krishnan Ramachandran, Jeffrey H. Y. Lum, Cheng Ean C
    Gastric Cancer.2023; 26(3): 393.     CrossRef
  • Genetic and immune microenvironment characterization of HER2‐positive gastric cancer: Their association with response to trastuzumab‐based treatment
    Hyun Jung Kwon, Yujun Park, Soo Kyung Nam, Enoch Kang, Ka‐Kyung Kim, Inhae Jeong, Yoonjin Kwak, Jeesun Yoon, Tae‐Yong Kim, Keun‐Wook Lee, Do‐Youn Oh, Seock‐Ah Im, Seong‐Ho Kong, Do Joong Park, Hyuk‐Joon Lee, Hyung‐Ho Kim, Han‐Kwang Yang, Hye Seung Lee
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Prevalence and Clinicopathological Significance of MET Overexpression and Gene Amplification in Patients with Gallbladder Carcinoma
Yeseul Kim, Seong Sik Bang, Seungyun Jee, Sungeon Park, Su-Jin Shin, Kiseok Jang
Cancer Res Treat. 2020;52(2):481-491.   Published online October 24, 2019
DOI: https://doi.org/10.4143/crt.2019.370
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Mesenchymal epithelial transition (MET) is a proto-oncogene that encodes a heterodimeric transmembrane receptor tyrosine kinase for the hepatocyte growth factor. Aberrant MET signaling has been described in several solid tumors—especially non-small cell lung cancer— and is associated with tumor progression and adverse prognosis. As MET is a potential therapeutic target, information regarding its prevalence and clinicopathological relevance is crucial.
Materials and Methods
We investigated MET expression and gene amplification in 113 gallbladder cancers using tissue microarray. Immunohistochemistry was used to evaluate MET overexpression, and silver/fluorescence in situ hybridization (ISH) was used to assess gene copy number.
Results
MET overexpression was found in 37 cases of gallbladder carcinoma (39.8%), and gene amplification was present in 17 cases (18.3%). MET protein expression did not correlate with MET amplification. MET amplification was significantly associated with aggressive clinicopathological features, including high histological grade, advanced pT category, lymph node metastasis, and advanced American Joint Committee on Cancer stage. There was no significant correlation between any clinicopathological factors and MET overexpression. No difference in survival was found with respect to MET overexpression and amplification status.
Conclusion
Our data suggested that MET might be a potential therapeutic target for targeted therapy in gallbladder cancer, because MET amplification was found in a subset of tumors associated with adverse prognostic factors. Detection of MET amplification by ISH might be a useful predictive biomarker test for anti-MET therapy.

Citations

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Pancreatic High-Grade Neuroendocrine Neoplasms in the Korean Population: A Multicenter Study
Haeryoung Kim, Soyeon An, Kyoungbun Lee, Sangjeong Ahn, Do Youn Park, Jo-Heon Kim, Dong-Wook Kang, Min-Ju Kim, Mee Soo Chang, Eun Sun Jung, Joon Mee Kim, Yoon Jung Choi, So-Young Jin, Hee Kyung Chang, Mee-Yon Cho, Yun Kyung Kang, Myunghee Kang, Soomin Ahn, Youn Wha Kim, Seung-Mo Hong, on behalf of the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists
Cancer Res Treat. 2020;52(1):263-276.   Published online July 12, 2019
DOI: https://doi.org/10.4143/crt.2019.192
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The most recent 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNENs) has refined the three-tiered 2010 scheme by separating grade 3 pancreatic neuroendocrine tumors (G3 PanNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). However, differentiating between G3 Pan- NETs and PanNECs is difficult in clinical practice.
Materials and Methods
Eighty-two surgically resected PanNENs were collected from 16 institutions and reclassified according to the 2017 WHO classification based on the histological features and proliferation index (mitosis and Ki-67). Immunohistochemical stains for ATRX, DAXX, retinoblastoma, p53, Smad4, p16, and MUC1 were performed for 15 high-grade PanNENs.
Results
Re-classification resulted in 20 G1 PanNETs (24%), 47 G2 PanNETs (57%), eight G3 well-differentiated PanNETs (10%), and seven poorly differentiated PanNECs (9%). PanNECs showed more frequent diffuse nuclear atypia, solid growth patterns and apoptosis, less frequent organoid growth and regular vascular patterns, and absence of low-grade PanNET components than PanNETs. The Ki-67 index was significantly higher in PanNEC (58.2%± 15.1%) compared to G3 PanNET (22.6%±6.1%, p < 0.001). Abnormal expression of any two of p53, p16, MUC1, and Smad4 could discriminate PanNECs from G3 PanNETs with 100% specificity and 87.5% sensitivity.
Conclusion
Histological features supporting the diagnosis of PanNECs over G3 PanNETs were the absence of a low-grade PanNET component in the tumor, the presence of diffuse marked nuclear atypia, solid growth pattern, frequent apoptosis and markedly increased proliferative activity with homogeneous Ki-67 labeling. Immunohistochemical stains for p53, p16, MUC1, and Smad4 may be helpful in distinguishing PanNECs from G3 PanNETs in histologically ambiguous cases, especially in diagnostic practice when only small biopsied tissues are available.

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High-Throughput Multiplex Immunohistochemical Imaging of the Tumor and Its Microenvironment
Jiwon Koh, Yoonjin Kwak, Jin Kim, Woo Ho Kim
Cancer Res Treat. 2020;52(1):98-108.   Published online May 27, 2019
DOI: https://doi.org/10.4143/crt.2019.195
AbstractAbstract PDFPubReaderePub
Purpose
The aim of this study was to develop a formalin-fixed paraffin-embedded (FFPE) tissue based multiplex immunochemistry (mIHC) method for high-throughput comprehensive tissue imaging and demonstrate its feasibility, validity, and usefulness.
Materials and Methods
The mIHC protocol was developed and tested on tissue microarray slides made from archived gastric cancer (GC) tissue samples. On a single FFPE slide, cyclic immunochemistry for multiple markers of immune cells and cytokeratin for tumor cells was performed; hematoxylin staining was used for demarcation of nuclei. Whole slides were digitally scanned after each cycle. For interpretation of mIHC results, we performed computer-assisted image analysis using publicly available software.
Results
Using mIHC, we were able to characterize the tumor microenvironment (TME) of GCs with accurate visualization of various immune cells harboring complex immunophenotypes. Spatial information regarding intratumoral and peritumoral TME could be demonstrated by digital segmentation of image guided by cytokeratin staining results. We further extended the application of mIHC by showing that subcellular localization of molecules can be achieved by image analysis of mIHC results.
Conclusion
We developed a robust method for high-throughput multiplex imaging of FFPE tissue slides. The feasibility and adaptability of mIHC suggest that it is an efficient method for in situ single-cell characterization and analysis.

Citations

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Discordance of the PAM50 Intrinsic Subtypes Compared with Immunohistochemistry-Based Surrogate in Breast Cancer Patients: Potential Implication of Genomic Alterations of Discordance
Hee Kyung Kim, Kyung Hee Park, Youjin Kim, Song Ee Park, Han Sang Lee, Sung Won Lim, Jang Ho Cho, Ji-Yeon Kim, Jeong Eon Lee, Jin Seok Ahn, Young-Hyuck Im, Jong Han Yu, Yeon Hee Park
Cancer Res Treat. 2019;51(2):737-747.   Published online September 5, 2018
DOI: https://doi.org/10.4143/crt.2018.342
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We aimed to analyze the discordance between immunohistochemistry (IHC)-based surrogate subtyping and PAM50 intrinsic subtypes and to assess overall survival (OS) according to discordance.
Materials and Methods
A total of 607 patients were analyzed. Hormone receptor (HR) expression was evaluated by IHC, and human epidermal growth factor receptor 2 (HER2) expression was analyzed by IHC and/or fluorescence in situ hybridization. PAM50 intrinsic subtypes were determined according to 50 cancer genes using the NanoString nCounter Analysis System. We matched concordant tumor as luminal A and HR+/HER2–, luminal B and HR+/HER2+, HR–/HER2+ and HER2–enriched, and triple-negative breast cancer (TNBC) and normal- or basal-like. We used Ion Ampliseq Cancer Panel v2 was used to identify the genomic alteration related with discordance. The Kaplan-Meier method was used to estimate OS.
Results
In total, 233 patients (38.4%) were discordant between IHC-based subtype and PAM50 intrinsic subtype. Using targeted sequencing, we detected somatic mutation–related discordant breast cancer including the VHL gene in the HR+/HER2– group (31% in concordant group, 0% in discordant group, p=0.03) and the IDH and RET genes (7% vs. 12%, p=0.02 and 0% vs. 25%, p=0.02, respectively) in the TNBC group. Among the luminal A/B patients with a discordant result had significantly worse OS (median OS, 73.6 months vs. not reached; p < 0.001), and among the patients with HR positivity, the basal-like group as determined by PAM50 showed significantly inferior OS compared to other intrinsic subtypes (5-year OS rate, 92.2% vs. 75.6%; p=0.01).
Conclusion
A substantial portion of patients showed discrepancy between IHC subtype and PAM50 intrinsic subtype in our study. The survival analysis demonstrated that current IHC-based classification could mislead the treatment and result in poor outcome. Current guidelines for IHC might be updated accordingly.

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The Clinical Value of PELP1 for Breast Cancer: A Comparison with Multiple Cancers and Analysis in Breast Cancer Subtypes
Xingen Wang, Julia Y. S. Tsang, Michelle A Lee, Yun-Bi Ni, Joanna H Tong, Siu-Ki Chan, Sai-Yin Cheung, Ka Fai To, Gary M Tse
Cancer Res Treat. 2019;51(2):706-717.   Published online August 23, 2018
DOI: https://doi.org/10.4143/crt.2018.316
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Proline, glutamic acid, and leucine-rich protein 1 (PELP1), a novel nuclear receptor (NR) co-regulator, is highly expressed in breast cancer. We investigated its expression in breast cancer subtypes, in comparison with other breast markers as well as cancers from different sites. Its prognostic relevance with different subtypes and other NR expression was also examined in breast cancers.
Methods
Immunohistochemical analysis was performed on totally 1,944 cancers from six different organs.
Results
PELP1 expression rate was the highest in breast cancers (70.5%) among different cancers. Compared to GATA3, mammaglobin and gross cystic disease fluid protein 15, PELP1 was less sensitive than GATA3 for luminal cancers, but was the most sensitive for non-luminal cancers. PELP1 has low expression rate (<20%) in colorectal cancers, gastric cancers and renal cell carcinomas, but higher in lung cancers (49.1%) and ovarian cancers (42.3%). In breast cancer, PELP1 expression was an independent adverse prognostic factor for non-luminal cancers (disease-free survival [DFS]: hazard ratio [HR], 1.403; p=0.012 and breast cancer specific survival [BCSS]: HR, 1.443; p=0.015). Interestingly, its expression affected the prognostication of androgen receptor (AR). ARposPELP1lo luminal cancer showed the best DFS (log-rank=8.563, p=0.036) while ARnegPELP1hi non-luminal cancers showed the worst DFS (log-rank=9.536, p=0.023).
Conclusion
PELP1 is a sensitive marker for breast cancer, particularly non-luminal cases. However, its considerable expression in lung and ovarian cancers may limit its utility in differential diagnosis in some scenarios. PELP1 expression was associated with poor outcome in non-luminal cancers and modified the prognostic effects of AR, suggesting the potential significance of NR co-regulator in prognostication.

Citations

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  • Trichorhinophalangeal Syndrome Type 1 Is a Highly Sensitive and Specific Marker for Diagnosing Triple-Negative Breast Carcinomas on Cytologic Samples
    Terrance J. Lynn, Jianhui Shi, Haiyan Liu, Sara E. Monaco, Jeffrey W. Prichard, Fan Lin
    Archives of Pathology & Laboratory Medicine.2024; 148(1): e1.     CrossRef
  • Value of Proline, Glutamic Acid, and Leucine-Rich Protein 1 and GATA Binding Protein 3 Expression in Breast Cancer: An Immunohistochemical study
    Manar Moustafa, Magdy Ismael, Salah Mohamed, Abeer M. Hafez
    Indian Journal of Surgery.2023; 85(3): 608.     CrossRef
  • MiR-195-5p is involved in testicular ischemia/reperfusion injury by directly targeting PELP1 and regulating spermatogonia pyroptosis
    KAI-XIANG HE, LIZHE XU, JIN-ZHUO NING, FAN CHENG
    International Immunopharmacology.2023; 121: 110427.     CrossRef
  • Estrogen Receptor Signaling in Breast Cancer
    Paulina Miziak, Marzena Baran, Ewa Błaszczak, Alicja Przybyszewska-Podstawka, Joanna Kałafut, Jolanta Smok-Kalwat, Magdalena Dmoszyńska-Graniczka, Michał Kiełbus, Andrzej Stepulak
    Cancers.2023; 15(19): 4689.     CrossRef
  • Immunohistochemical study of proline, glutamic acid and leucine-rich protein 1 (PELP1) in correlation with guanine adenine thymine adenine family member 3 (GATA-3) receptors expression in breast carcinomas
    Ahmed A Elmetwally, Mennat Allah M Abdel-Hafeez, Makram M Hammam, Gamal A Hafez, Maha M Atwa, Mohammed K El-Kherbetawy
    Egyptian Journal of Pathology.2023; 43(1): 53.     CrossRef
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    Manar Moustafa, Magdy Ismael, Salah Mohamed, Abeer Magdy
    Revista de Senología y Patología Mamaria.2022; 35(3): 153.     CrossRef
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    Qingqing Ding, Lei Huo, Yan Peng, Esther C. Yoon, Zaibo Li, Aysegul A. Sahin
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    Xingen Wang, Weihua Yin, Li Liang
    Pathology - Research and Practice.2022; 237: 154065.     CrossRef
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    Dongmei Zhang, Jiali Dai, Yu Pan, Xiuli Wang, Juanjuan Qiao, Hironobu Sasano, Baoshan Zhao, Keely M. McNamara, Xue Guan, Lili Liu, Yanzhi Zhang, Monica S. M. Chan, Shuwen Cao, Ming Liu, Sihang Song, Lin Wang
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    Hongzhu Yan, Yanling Sun, Qian Wu, Zhe Wu, Meichun Hu, Yuanpeng Sun, Yusi Liu, Zi Ma, Shangqin Liu, Wuhan Xiao, Fuxing Liu, Zhifeng Ning
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ALK Protein Expression Is Related to Neuroblastoma Aggressiveness But Is Not Independent Prognostic Factor
Ji Won Lee, Sung Hye Park, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin, Hyo Seop Ahn
Cancer Res Treat. 2018;50(2):495-505.   Published online May 22, 2017
DOI: https://doi.org/10.4143/crt.2016.577
AbstractAbstract PDFPubReaderePub
Purpose
In this study, anaplastic lymphoma kinase (ALK) mutation and amplification, ALK protein expression, loss of the nuclear alpha thalassemia/mental retardation syndrome X-linked (ATRX) protein, and telomerase reverse transcriptase (TERT) protein expressionwere studied to investigate potential correlations between these molecular characteristics and clinical features or outcomes in neuroblastoma.
Materials and Methods
Seventy-two patients were enrolled in this study. Polymerase chain reaction amplification and direct sequencing were used for mutation analysis. ALK and MYCN amplifications were detected by fluorescence in situ hybridization. Protein expressionwas evaluated by immunohistochemical (IHC) staining.
Results
ALK mutation was found in only two patients (4.1%); ALK amplification was not detected. ALK positivity, loss of nuclear ATRX protein, TERT positivity by IHC were detected in 40 (55.6%), nine (13.0%), and 42 (59.2%) patients, respectively. The incidence of ALK expression increased in accordance with increasing tumor stage (p=0.001) and risk group (p < 0.001). The relapse rate was significantly higher in ALK+ patients compared to that of other patients (47.5% vs. 11.3%, p=0.007). However, there was no significant difference in relapse rate when the survival analysis was confined to the high-risk patients.
Conclusion
Although ALK mutation was rare and no amplification was observed, ALK protein expression was found in a significant number of patients and was correlated with advanced stage and high-risk neuroblastoma. ALK protein expression could be considered as a marker related to the aggressive neuroblastoma, but it was not the independent prognostic factor for the outcome.

Citations

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  • Immunohistochemical expression of anaplastic lymphoma kinase in neuroblastoma and its relations with some clinical and histopathological features
    Thu Dang Anh Phan, Thao Quyen Nguyen, Nhi Thuy To, Thien Ly Thanh, Dat Quoc Ngo
    Journal of Pathology and Translational Medicine.2024; 58(1): 29.     CrossRef
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    Peng Hong, Zaihong Hu, Jie Lin, Kongkong Cui, Zhiqiang Gao, Xiaomao Tian, Qinlin Shi, Tao Lin, Guanghui Wei
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  • Prominent Staining of MYCN Immunohistochemistry Predicts a Poor Prognosis in MYCN Non-Amplified Neuroblastoma
    Manli Zhao, Weizhong Gu, Fei Liu, Lihua Yu, Yan Shu, Lei Liu, Jiahui Hu, Yang Liu, Hongfeng Tang, Jianhua Mao
    Pediatric and Developmental Pathology.2023; 26(2): 124.     CrossRef
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    Neha Bhardwaj, Manish Rohilla, Upasana Gautam, Amita Trehan, Deepak Bansal, Nandita Kakkar, Radhika Srinivasan
    American Journal of Clinical Pathology.2023;[Epub]     CrossRef
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    Current Enzyme Inhibition.2023; 19(2): 109.     CrossRef
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    World Neurosurgery.2022; 159: e48.     CrossRef
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    Dinesh Babu Somasundaram, Sheeja Aravindan, Nandita Gupta, Zhongxin Yu, Ashley Baker, Natarajan Aravindan
    World Journal of Pediatrics.2022; 18(4): 285.     CrossRef
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    Janina Baranowska-Kortylewicz, Zbigniew P. Kortylewicz, Erin M. McIntyre, John G. Sharp, Don W. Coulter
    Journal of Pediatric Hematology/Oncology.2022; 44(6): 293.     CrossRef
  • Differential Impact of ALK Mutations in Neuroblastoma
    Tara O'Donohue, Nitya Gulati, Audrey Mauguen, Brian H. Kushner, Neerav Shukla, M. I. Rodriguez-Sanchez, Nancy Bouvier, Stephen Roberts, Ellen Basu, Nai-Kong Cheung, Shakeel Modak
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    Daniel A. Morgenstern, Rochelle Bagatell, Susan L. Cohn, Michael D. Hogarty, John M. Maris, Lucas Moreno, Julie R. Park, Andrew D. Pearson, Gudrun Schleiermacher, Dominique Valteau‐Couanet, Wendy B. London, Meredith S. Irwin
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    Ricky Trigg, Suzanne Turner
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Predictive Value of Tertiary Lymphoid Structures Assessed by High Endothelial Venule Counts in the Neoadjuvant Setting of Triple-Negative Breast Cancer
In Hye Song, Sun-Hee Heo, Won Seon Bang, Hye Seon Park, In Ah Park, Young-Ae Kim, Suk Young Park, Jin Roh, Gyungyub Gong, Hee Jin Lee
Cancer Res Treat. 2017;49(2):399-407.   Published online July 27, 2016
DOI: https://doi.org/10.4143/crt.2016.215
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The tertiary lymphoid structure (TLS) is an important source of tumor-infiltrating lymphocytes (TILs), which have a strong prognostic and predictive value in triple-negative breast cancer (TNBC). A previous study reported that the levels of CXCL13 mRNA expression were associated with TLSs, but measuring the gene expression is challenging in routine practice. Therefore, this study evaluated the MECA79-positive high endothelial venule (HEV) densities and their association with the histopathologically assessed TLSs in biopsy samples. In addition, the relationship of TLSs with the CXCL13 transcript levels and clinical outcomes were examined.
Materials and Methods
A total of 108 TNBC patients treated with neoadjuvant chemotherapy (NAC) were studied. The amounts of TILs and TLSs were measured histopathologically using hematoxylin and eosin–stained slides. The HEV densities and TIL subpopulations were measured by immunohistochemistry for MECA79, CD3, CD8, and CD20. CXCL13 mRNA expression levels using a NanoString assay (NanoString Technologies).
Results
The mean number of HEVs in pre-NAC biopsies was 12 (range, 0 to 72). The amounts of TILs and TLSs, HEV density, and CXCL13 expression showed robust correlations with each other. A lower pre-NAC clinical T stage, higher TIL and TLS levels, a higher HEV density, CD20-positive cell density, and CXCL13 expression were significant predictors of a pathologic complete response (pCR). Higher CD8-positive cell density and levels of CXCL13 expression were significantly associated with a better disease-free survival rate.
Conclusion
MECA79-positive HEV density in pre-NAC biopsies is an objective and quantitative surrogate marker of TLS and might be a valuable tool for predicting pCR of TNBC in routine pathology practice.

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A New Cell Block Method for Multiple Immunohistochemical Analysis of Circulating Tumor Cells in Patients with Liver Cancer
Soo Jeong Nam, Hyun Yang Yeo, Hee Jin Chang, Bo Hyun Kim, Eun Kyung Hong, Joong-Won Park
Cancer Res Treat. 2016;48(4):1229-1242.   Published online March 30, 2016
DOI: https://doi.org/10.4143/crt.2015.500
AbstractAbstract PDFPubReaderePub
Purpose
We developed a new method of detecting circulating tumor cells (CTCs) in liver cancer patients by constructing cell blocks from peripheral blood cells, including CTCs, followed by multiple immunohistochemical analysis.
Materials and Methods
Cell blockswere constructed from the nucleated cell pellets of peripheral blood afterremoval of red blood cells. The blood cell blocks were obtained from 29 patients with liver cancer, and from healthy donor blood spikedwith seven cell lines. The cell blocks and corresponding tumor tissues were immunostained with antibodies to seven markers: cytokeratin (CK), epithelial cell adhesion molecule (EpCAM), epithelial membrane antigen (EMA), CK18, α-fetoprotein (AFP), Glypican 3, and HepPar1.
Results
The average recovery rate of spiked SW620 cells from blood cell blocks was 91%. CTCs were detected in 14 out of 29 patients (48.3%); 11/23 hepatocellular carcinomas (HCC), 1/2 cholangiocarcinomas (CC), 1/1 combined HCC-CC, and 1/3 metastatic cancers. CTCs from 14 patients were positive for EpCAM (57.1%), EMA (42.9%), AFP (21.4%), CK18 (14.3%), Gypican3 and CK (7.1%, each), and HepPar1 (0%). Patients with HCC expressed EpCAM, EMA, CK18, and AFP in tissue and/or CTCs, whereas CK, HepPar1, and Glypican3 were expressed only in tissue. Only EMA was significantly associated with the expressions in CTC and tissue. CTC detection was associated with higher T stage and portal vein invasion in HCC patients.
Conclusion
This cell block method allows cytologic detection and multiple immunohistochemical analysis of CTCs. Our results show that tissue biomarkers of HCC may not be useful for the detection of CTC. EpCAM could be a candidate marker for CTCs in patients with HCC.

Citations

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Association between Mutation and Expression of TP53 as a Potential Prognostic Marker of Triple-Negative Breast Cancer
Ji-Yeon Kim, Kyunghee Park, Hae Hyun Jung, Eunjin Lee, Eun Yoon Cho, Kwang Hee Lee, Soo Youn Bae, Se Kyung Lee, Seok Won Kim, Jeong Eon Lee, Seok Jin Nam, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
Cancer Res Treat. 2016;48(4):1338-1350.   Published online February 18, 2016
DOI: https://doi.org/10.4143/crt.2015.430
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
TP53, the most frequently mutated gene in breast cancer, is more frequently altered in HER2-enriched and basal-like breast cancer. However, no studies have clarified the role of TP53 status as a prognostic and predictive marker of triple-negative breast cancer (TNBC).
Materials and Methods
We performed p53 immunohistochemistry (IHC), nCounter mRNA expression assay, and DNA sequencing to determine the relationship between TP53 alteration and clinical outcomes of TNBC patients.
Results
Seventy-seven of 174 TNBC patients were found to harbor a TP53 mutation. Patients with missense mutations showed high protein expression in contrast to patients with deletion mutations (positivity of IHC: wild type vs. missense vs. deletion mutation, 53.6% vs. 89.8% vs. 25.0%, respectively; p < 0.001). TP53 mRNA expression was influenced by mutation status (mRNA expression [median]: wild type vs. missense vs. deletion mutation, 207.36± 132.73 vs. 339.61±143.21 vs. 99.53±99.57,respectively; p < 0.001). According to survival analysis, neither class of mutation nor protein or mRNA expression status had any impact on patient prognosis. In subgroup analysis, low mRNA expression was associated with poor prognosis in patientswith a TP53 missense mutation (5-year distantrecurrence-free survival [5Y DRFS]: low vs. high, 50.0% vs. 87.8%; p=0.009), while high mRNA expression with a TP53 deletion mutation indicated poor prognosis (5Y DRFS: low vs. high, 91.7% vs. 75.0%; p=0.316).
Conclusion
Association between TP53 mutation and expression indicates a potential prognostic marker of TNBC; hence both DNA sequencing and mRNA expression analysis may be required to predict the prognosis of TNBC patients.

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Prognostic Significance of Defining L-Cell Type on the Biologic Behavior of Rectal Neuroendocrine Tumors in Relation with Pathological Parameters
The Gastrointestinal Pathology Study Group of Korean Society of Pathologists, Jin Hee Sohn, Mee-Yon Cho, Yangsoon Park, Hyunki Kim, Woo Ho Kim, Joon Mee Kim, Eun Sun Jung, Kyoung-Mee Kim, Jae Hyuk Lee, Hee Kyung Chan, Do Youn Park, Mee Joo, Sujin Kim, Woo Sung Moon, Mi Seon Kang, So-Young Jin, Yun Kyung Kang, Sun Och Yoon, HyeSeung Han, EunHee Choi
Cancer Res Treat. 2015;47(4):813-822.   Published online February 26, 2015
DOI: https://doi.org/10.4143/crt.2014.238
AbstractAbstract PDFPubReaderePub
Purpose
In 2010, the World Health Organization categorized L-cell type neuroendocrine tumors (NETs) as tumors of uncertain malignancy, while all others were classified as malignant. However, the diagnostic necessity of L-cell immunophenotyping is unclear, as are tumor stage and grade that may guide diagnosis and management. To clarify the predictive markers of rectal neuroendocrine neoplasms (NENs), 5- and 10-year overall survival (OS) was analyzed by pathological parameters including L-cell phenotype. Materials and Methods A total of 2,385 rectal NENs were analyzed from our previous multicenter study and a subset of 170 rectal NENs was immunophenotyped.
Results
In univariate survival analysis, tumor grade (p < 0.0001), extent (p < 0.0001), size (p < 0.0001), lymph node metastasis (p=0.0063), and L-cell phenotype (p < 0.0001) showed significant correlation with the prognosis of rectal NENs; however, none of these markers achieved independent significance in multivariate analysis. The 10-year OS of tumors of NET grade 1, < 10 mm, the mucosa/submucosa was 97.58%, 99.47%, and 99.03%, respectively. L-Cell marker, glucagon II (GLP-1&2), with a cut off score of > 10, is useful in defining L-Cell type. In this study, an L-cell immunophenotype was found in 83.5% of all rectal NENs and most, but not all L-cell type tumors were NET G1, small (< 10 mm) and confined to the mucosa/submucosa. Conclusion From these results, the biological behavior of rectal NENs does not appear to be determined by L-cell type alone but instead by a combination of pathological parameters.

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Identification of EGFR Mutations by Immunohistochemistry with EGFR Mutation–Specific Antibodies in Biopsy and Resection Specimens from Pulmonary Adenocarcinoma
Chi Hong Kim, Seung Hoon Kim, Sonya Youngju Park, Jinyoung Yoo, Sung Kyoung Kim, Hoon Kyo Kim
Cancer Res Treat. 2015;47(4):653-660.   Published online January 30, 2015
DOI: https://doi.org/10.4143/crt.2014.118
AbstractAbstract PDFPubReaderePub
Purpose
Mutation-specific antibodies have recently been developed for identification of epidermal growth factor receptor (EGFR) mutations by immunohistochemistry (IHC). This study was designed to investigate whether the type of specimen (biopsy vs. resection) would make a difference in determining mutation status by IHC, and to evaluate whether biopsies are suitable for detection of mutant EGFR protein.
Materials and Methods
IHC was performed using mutation-specific antibodies for E746-A750 deletion (DEL) and L858R point mutation (L858R) in biopsies and tissue microarrays of resected tumors from 154 patients with pulmonary adenocarcinoma. Results were then compared with DNA sequencing data.
Results
Molecular-based assays detected EGFR mutations in 62 patients (40.3%), including 14 (9.1%) with DEL, and 31 (20.1%) with L858R. IHC with two mutation-specific antibodies showed a homogeneous staining pattern, and correctly identified EGFRmutation status in 89% (137/154). Overall (biopsy/resection) sensitivity, specificity, positive predictive value, and negative predictive value were 75.6% (78.3%/72.7%), 94.5% (90.9%/96.3%), 85% (78.3%/88.9%), and 90.4% (90.9%/89.7%), respectively.
Conclusion
Our data showed that IHC using EGFR mutation–specific antibodies is useful for detection of EGFRmutations with high specificity and good sensitivity not only for resection specimens but also for biopsy materials. Therefore, IHC using EGFRmutation–specific antibodies may preclude a second biopsy procedure to obtain additional tissues for identification of EGFR mutations by molecular assays in biopsies from advanced cancer, particularly when tumor cells in the samples are limited.

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    Oncotarget.2016; 7(50): 82876.     CrossRef
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Clinicopathological and Immunohistochemical Features of Gastointestinal Stromal Tumors
Yu Na Kang, Hye Ra Jung, Ilseon Hwang
Cancer Res Treat. 2010;42(3):135-143.   Published online September 30, 2010
DOI: https://doi.org/10.4143/crt.2010.42.3.135
AbstractAbstract PDFPubReaderePub
Purpose

The purpose of this study was to evaluate the clinicopathological features and immunohistochemical features of gastrointestinal stromal tumor (GIST), and specifically the expressions of platelet derived growth factor receptor A (PDGFRA), protein kinase C theta (PKC theta), discovered on GIST-1 (DOG-1), p16 and p27.

Materials and Methods

Total 118 patients who underwent surgical resection for GIST at our institution between Jan 1997 and Dec 2007 were retrospectively studied. Immunohistochemical staining for c-kit, PDGFRA, PKC-theta, DOG-1, p16 and p27 was performed on a tissue microarray of the 118 GIST. The clinicopathologic parameters, the disease-free survival (DFS) and the overall survival rate were analyzed along with immunohistochemistry.

Results

The immunohistochemical stains for c-kit, CD34, PKC-theta, PDGFRA, DOG-1, p16 and p27 were positive in 89.8%, 72.0%, 56.8%, 94.9%, 90.7%, 69.5% and 44.1% of the tumor samples, respectively. The immunohistochemical expression of c-kit was strongly correlated with PKC-theta (p=0.000), DOG-1 (p=0.000) and CD34 (p=0.002). The DFS rate was significantly decreased for the patients with peritoneal GIST, high risk GIST, ≥10 cm-sized GIST, ≥10 mitoses/50 high power fields (HPFs) and p16 positivity (p=0.001, p=0.004, p=0.001, p=0.003 and p=0.028). GISTs ≥10 cm, epithelioid tumor cell type, and c-kit, and DOG-1 negativity were significantly associated with shorter period of overall survival (p=0.048, p=0.006, p=0.000 and p=0.000).

Conclusion

The expression of p16 and no expression of c-kit and DOG-1 in GISTs, as well as peritoneal tumor site, high risk group, large tumor size, epithelioid tumor cell type and numerous mitoses, may be potentially prognostic factors for predicting worse outcome for patients who suffer from GIST.

Citations

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Clinical Significance of Lymph Node Micrometastasis in Stage I and II Colon Cancer
Sun Jin Park, Kil Yeon Lee, Si Young Kim
Cancer Res Treat. 2008;40(2):75-80.   Published online June 30, 2008
DOI: https://doi.org/10.4143/crt.2008.40.2.75
AbstractAbstract PDFPubReaderePub
Purpose

A 25% rate of recurrence after performing complete resection in node-negative colon cancer patients suggests that their nodal staging is frequently suboptimal. Moreover, the value of occult cancer cells in tumor-free lymph nodes still remains uncertain. The authors evaluated the prognostic significance of the pathologic parameters, including the lymph node occult disease (micrometastases) detected by immunohistochemistry, in patients with node-negative colon cancer.

Materials and Methods

The study included 160 patients with curatively resected stage I or II colon cancer and they were without rectal cancer. 2852 lymph nodes were re-examined by re-do hematoxylin and eosin (H-E) staining and immunohistochemical staining. The detection rates were compared with the clinicopathologic characteristics and with the cancer-specific survival.

Results

Occult metastases were detected in 8 patients (5%). However, no clinicopathologic parameter was found to be correlated with the presence of micrometastasis. Twenty patients developed recurrence at a median follow-up of 45.7 months: 14 died of colon cancer and 9 died from noncancer-related causes. Univariate analysis showed that lymphatic invasion and the number of retrieved lymph nodes significantly influenced survival, and multivariate analysis revealed that the stage, the number of retrieved lymph nodes and lymphatic invasion were independently related to the prognosis.

Conclusions

Inadequate lymph node retrieval and lymphatic invasion were found to be associated with a poorer outcome for node-negative colon cancer patients. The presence of immunostained tumors cells in pN0 lymph nodes was found to have no significant effect on survival, but these tumor were identified by re-do H-E staining. Maximal attention should be paid to the total number of lymph nodes that are retrieved during surgery for colon cancer patients.

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Prognostic Significance of Immunohistochemical Expression of p53 Gene Product in Operable Breast Cancer
Hong Suk Song, Young Rok Do, Sun Hee Kang, Ki Yong Jeong, Yu Sa Kim
Cancer Res Treat. 2006;38(4):218-223.   Published online December 31, 2006
DOI: https://doi.org/10.4143/crt.2006.38.4.218
AbstractAbstract PDFPubReaderePub
Purpose

The aim of this study was to investigate the prognostic significance of the expression of p53 gene product in operable invasive breast cancer by performing immunohistochemical analysis.

Materials and Methods

Between January 1993 and December 2001, 440 operable invasive breast cancer patients underwent immunohistochemical staining for p53, and we retrospectively analyzed these results together with the clinical outcomes.

Results

The overexpression of p53 was detected in 51.6% of the cases. The overexpression of p53 was inversely correlated with lymph node metastasis (p=0.005). The tumor size, tumor histology, histologic grade, hormonal receptor status and tumor stage were not related to the overexpression of p53. Multivariate Cox regression analysis indicate that lymph node metastasis, tumor size and the p53 expression were the significant prognostic factors for overall survival; lymph node metastasis, the estrogen receptor status and the p53 expression were the significant prognostic factors for relapse free survival. On the subgroup analysis, the p53 non-expressors showed better 7-year overall survival (92.7% vs. 76.7%, respectively, p=0.011) and relapse free survival (74.9% vs. 57.8%, respectively, p=0.032) than did the p53 overexpressors for the patients with lymph node metastasis. However, for the patients without lymph node metastasis, the survival rates were not different for both the p53 non-expressors and the p53 overexpressors.

Conclusion

Immunohistochemical staining of the p53 gene product was an independent prognostic factor for predicting survival of the lymph node positive invasive breast cancer patients.

Citations

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    Asim Kumar Manna, Aparajita Samaddar, Sumit Mitra, Swapan Pathak, Srabani Chakrabarti, Diptendra Kumar Sarkar
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    Ji‐Youn Sung, Ranah Kim, Ja‐Eun Kim, Juhie Lee
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Review Article
Tissue Array Methods for High-throughput Clinicopathologic Research
Hye Seung Lee, Woo Ho Kim
Cancer Res Treat. 2006;38(1):1-6.   Published online February 28, 2006
DOI: https://doi.org/10.4143/crt.2006.38.1.1
AbstractAbstract PDFPubReaderePub

Recent research in molecular biology has identified a significant number of novel markers, which may have diagnostic, prognostic and therapeutic significance. High-throughput tissue array method facilitates the validation of novel markers by enabling the simultaneous analysis of hundreds or thousands of tissue specimens. Tissue array slides can be analyzed using techniques such as immunohistochemistry and in situ hybridization. In this review, we give a brief overview of tissue array method and its application to high throughput clinicopathologic research.

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Original Articles
Expressions of Matrix Metalloproteinase-7 and -9 and their Prognostic Significances in Rectal Cancer
Young Rak Cho, Hyuk-Chan Kwon, Sung-Hwan Suh, Jong Hoon Lee, Sung-Hyun Kim, Hong-Jo Choi, Hyung-Sik Lee, Mee Sook Roh, Tae-Ho Hwang, Jae-Seok Kim, Hyo-Jin Kim
Cancer Res Treat. 2005;37(6):354-359.   Published online December 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.6.354
AbstractAbstract PDFPubReaderePub
Purpose

The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes. MMPs are known to be involved in tumor invasion, and several have been implicated in tumor prognosis. The aim of this study was to evaluate the prognostic significances of the expressions of MMP-7 and -9 in rectal cancer.

Materials and Methods

The tumor tissues of 87 patients with stage II or III rectal carcinoma that underwent potentially curative resection followed by postoperative adjuvant chemoradiation and 5-fluorouracil based chemotherapy, were investigated immunohistochemically using monoclonal antibodies against MMP-7 and MMP-9. Clinical information, including tumor grades, carcinoembryonic antigen (CEA) levels, and disease-free survival and overall survival were evaluated with respect to the expressions of MMP-7 and -9.

Results

Median follow-up duration was 53.2 months, and median patient age was 55±11 years (range 32~75). MMP-7 expression in tumor tissue was found to be significantly correlated with the presence of nodal metastasis (p=0.029), whilst MMP-9 expression correlated with depth of tumor invasion (p=0.019). No relationships were found between the expressions of MMP-7 or -9 and age, sex, tumor size, tumor grade, or CEA level. Univariate analysis showed that MMP-7 expression was associated with poor 5-year overall survival (12.8 months vs. 65.3 months, p=0.0405). Multivariate analysis confirmed that MMP-7 was independently associated with an adverse outcome (Relative risk: 1.415, p=0.027). However, MMP-9 expression was not found to be related to clinical outcome.

Conclusion

MMP-7 expression in tumor tissue is associated with lymph node metastasis and a poor 5-year overall survival in rectal cancer patients.

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    Nora Sundahl, Fréderic Duprez, Piet Ost, Wilfried De Neve, Marc Mareel
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Expression of Maspin is associated with the Intestinal Type of Gastric Adenocarcinoma
Seong Man Kim, Seong Jin Cho, Woo Young Jang, Duck Hwan Kim, Hyung Sik Shin, Myoung Kuk Jang, Hak Yang Kim, Eun Sook Nam
Cancer Res Treat. 2005;37(4):228-232.   Published online August 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.4.228
AbstractAbstract PDFPubReaderePub
Purpose

Maspin is known as a tumor suppressor gene, but its significance has been questioned in various human cancers. The aim of this study was to investigate the expression pattern of Maspin in human gastric adenocarcinomas and its possible correlation with clinicopathological findings.

Materials and Methods

The expression of Maspin mRNA was measured by nested RT-PCR using 60 frozen adenocarcinomas of the stomach and 31 noncancerous tissues from the proximal resection margin. Immunohistochemical study for Maspin protein expression was carried out using 62 paraffin-embedded tissues, composed of both cancer and noncancerous tissues.

Results

Maspin mRNA expression was detected in 80.0% (48 of 60) of the gastric adenocarcinomas, but in only 22.6% (7 of 31) of the normal gastric mucosa (p<0.001). The positive rate of Maspin protein expression was higher in the adenocarcinomas than the normal tissues (62.9% vs. 27.4%, p<0.05). In addition, the intestinal type of tumors showed significantly higher expression levels compared to the diffuse type of tumors (81.5% vs. 48.6%, p<0.05).

Conclusion

Our results suggest that Maspin is frequently expressed in human gastric cancers, and its expression might be associated with tumorigenesis of the intestinal type of gastric cancer.

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Co-Expression of Cox-2, C-Met and β-catenin in Cells Forming Invasive front of Gallbladder Cancer
Woo Sung Moon, Ho Sung Park, Ho Lee, Rama Pai, Andrzej S. Tarnawski, Kyung Ryoul Kim, Kyu Yun Jang
Cancer Res Treat. 2005;37(3):171-176.   Published online June 30, 2005
DOI: https://doi.org/10.4143/crt.2005.37.3.171
AbstractAbstract PDFPubReaderePub
Purpose

Gallbladder cancer is a malignancy with poor prognosis, predominantly resulting from invasion and metastasis. Our previous studies have demonstrated that prostaglandin E2 (PGE2), generated by cyclooxygenase 2 (Cox-2), transactivates epidermal growth factor receptor (EGFR), c-Met and β-catenin; thus, enhancing colon cancer cell growth and invasiveness in vitro. To determine whether these findings are applicable to clinical conditions, we examined the expression and cellular localization/co-localization of Cox-2, c-Met, β-catenin, EGFR and c-erbB2 in gallbladder cancer.

Materials and Methods

Thirty-five specimens of invasive gallbladder cancer, 8 in situ carcinoma and 7 adenoma specimens were immunostained with specific antibodies against Cox-2, c-Met, β-catenin, EGFR and c-erbB2. The cellular distribution, localization and colocalization were examined, and the signal intensities quantified in: a) the central area of gallbladder cancer and b) cancer cells forming the invasive front.

Results

Cox-2, c-Met, β-catenin, c-erbB2 and EGFR were over-expressed in 80, 74, 71, 62 and 11% of invasive gallbladder cancers, respectively. β-catenin was expressed in 80% of non-malignant specimens, exclusively in the cell membrane, while the cancer specimens showed cytoplasmic and/or nuclear staining. Significantly higher Cox-2, c-Met and β-catenin expressions were present in cancer cells of the invasive front than in the tumor central areas (p<0.001), and these expressions were significantly (p=0.01) associated with the invasion depth. Co-expressions of Cox-2, c-Met, β-catenin and c-erbB2 were present in 42% of the specimens in cancer cells forming the invasive front.

Conclusion

The overexpressions, and often co-localizations, of Cox-2, c-Met and β-catenin in cancer cells forming the invasive front indicate their local interactions and important roles in invasion.

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Loss of DNA-dependent Protein Kinase Catalytic Subunit (DNA-PKcs) Expression in Gastric Cancers
Hye Seung Lee, Han-Kwang Yang, Woo Ho Kim, Gheeyoung Choe
Cancer Res Treat. 2005;37(2):98-102.   Published online April 30, 2005
DOI: https://doi.org/10.4143/crt.2005.37.2.98
AbstractAbstract PDFPubReaderePub
Purpose

DNA-PKcs is one of the DNA repair genes. It was recently found that hyperplasia and dysplasia of the intestinal mucosa and the production of aberrant crypt foci were developed in DNA-PKcs-null mice, and this suggests a suppressive role for DNA-PKcs in tumorigenesis.

Materials and Methods

To investigate the possible relationship between the clinico-pathologic characteristics and the survival of gastric cancer patients, the expression status of DNA-PKcs was determined in 279 consecutive gastric cancers. Immunohistochemical analysis was performed to evaluate the expression levels of DNA-PKcs protein by using the tissue array method.

Results

Out of 279 consecutive gastric cancers, 63 cases (22.6%) showed the loss of DNA-PKcs expression. The loss of DNA-PKcs expression was significantly associated with advanced cancer (p<0.001), lymphatic invasion (p=0.001), lymph node metastasis (p=0.009), and advanced pTNM stage (p=0.009). Univariate survival analysis revealed that patients with the loss of DNA-PKcs expression had significantly poorer survival than those patients with intact DNA-PKcs expression (p=0.004). Moreover, the loss of DNA-PKcs expression was identified to correlate with a lower survival in the subgroup of stage I gastric cancer patients (p=0.037).

Conclusion

The loss of DNA-PKcs expression was found in 23% of human gastric cancers and this was identified to significantly correlate with poor patient survival, especially for stage I gastric cancer patients.

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Prognostic Significance of CD24 Expression in Gastric Carcinoma
Nevine S. Darwish, Min A Kim, Mee Soo Chang, Hye Seung Lee, Byung Lan Lee, Yong Il Kim, Woo Ho Kim
Cancer Res Treat. 2004;36(5):298-302.   Published online October 30, 2004
DOI: https://doi.org/10.4143/crt.2004.36.5.298
AbstractAbstract PDFPubReaderePub
Purpose

The human CD24 antigen is a small heavily glycosylated cell surface protein, which is expressed in hematological malignancies, as well as in a large variety of solid tumors. Its expression is now known to be related to the prognosis of several kinds of tumors. This study is designed to examine the prognostic significance of CD24 in Korean gastric cancer patients.

Materials and Methods

In the present study, we examined CD24 expression in 300 consecutive cases of gastric carcinoma by immunohistochemical staining using the tissue-array method. We also investigated the clinicopathological profiles related to CD24 expression.

Results

One hundred and three cases out of 300 (34.3%) showed the positive expression of CD24. The altered expression of CD24 was significantly associated with differentiated cancer (p=0.003), the intestinal subtype according to the Lauren classification (p<0.001), the advanced stage cancer (p=0.027), with lymphatic invasion (p=0.038) and with vascular invasion (p=0.006). The survival analysis revealed that the patients with CD24 positive expression showed significantly poorer survival than those without CD24 expression. Moreover, a combined evaluation revealed that PTEN+/CD24- cases showed the best survival compared to other groups (p=0.01).

Conclusion

Positive CD24 expression occurs in a subset of gastric carcinomas and it correlates significantly with lymphatic invasion, blood vessel invasion and poor survival.

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    Mi Jeong Kwon, Jinil Han, Ji Hyun Seo, Kyoung Song, Hae Min Jeong, Jong-Sun Choi, Yu Jin Kim, Seon-Heui Lee, Yoon-La Choi, Young Kee Shin, Yves St-Pierre
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    Sormeh Mina, Benjamin A Bohn, Ronald Simon, Antje Krohn, Matthias Reeh, Dirk Arnold, Carsten Bokemeyer, Guido Sauter, Jakob R Izbicki, Andreas Marx, Phillip R Stahl
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    Hye Seung Lee, Woo Ho Kim
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Prognostic Significance of Immunohistochemical Expression of EGFR and C-erbB-2 Oncoprotein in Curatively Resected Gastric Cancer
Hong Suk Song, Young Rok Do, In Ho Kim, Soo Sang Sohn, Kun Young Kwon
Cancer Res Treat. 2004;36(4):240-245.   Published online August 31, 2004
DOI: https://doi.org/10.4143/crt.2004.36.4.240
AbstractAbstract PDFPubReaderePub
Purpose

The purpose of this study was to investigate the prognostic significance of the expression of EGFR and C-erbB-2 gene products by immunohistochemical analysis for curatively resected gastric adenocarcinoma.

Materials and Methods

Between January 1996 and December 2001, 739 patients with curatively resected gastric cancer patients underwent immunohistochemical staining for EGFR and C-erbB-2 proteins, and we retrospectively analyzed their correlation with the clinical outcome.

Results

The overexpressions of EGFR and C-erbB-2 were 25.4% and 26.2%, respectively. The overexpressions of EGFR was associated with the more poorly differentiated tumor (p=0.000) and with neuronal invasion (p=0.03). Overexpression of C-erbB-2 was associated with less vascular invasion (p=0.001). Tumor depth or node metastasis was not related to the overexpression of EGFR or C-erbB-2. The seven-year overall survival and relapse-free survival rates were 87.2% and 75.8%, respectively. Upon multivariate Cox regression analysis, the tumor stage, tumor size and patient age were important prognostic factors for overall survival, and tumor stage was the important factor for relapse-free survival. Overexpressions of EGFR or c-erbB-2 were not significant prognostic factors.

Conclusion

Immunohistochemical staining of EGFR and C-erbB-2 gene products were not independent prognostic factors for predicting the overall survival and the relapse-free survival in curatively resected gastric cancer.

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    Y. Wang, L. He, Y. Cheng
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    Roberto de Moraes Cordts Filho, Paulo Kassab, Laura Carolina Lopez Claro, Mabel Tatty de Medeiros Fracassi, Patrícia Colombo-Souza, Daniel Kenji Fukuhara, Fábio Rodrigues Thuler, Wilson Rodrigues de Freitas Junior, Elias Jirjoss Ilias, Carlos Alberto Malh
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Expression of c-kit and p53 in Non-small Cell Lung Cancers
Jinyoung Yoo, Chi Hong Kim, So Hyang Song, Byoung Yong Shim, Youn Ju Jeong, Meyung Im Ahn, Sung Whan Kim, Deog Gon Cho, Min Seop Jo, Kyu Do Cho, Hong Joo Cho, Hoon-Kyo Kim
Cancer Res Treat. 2004;36(3):167-172.   Published online June 30, 2004
DOI: https://doi.org/10.4143/crt.2004.36.3.167
AbstractAbstract PDFPubReaderePub
Purpose

Increasing experimental evidence indicates that abnormal expression of c-kit may be implicated in the pathogenesis of a variety of solid tumors. It has been reported that over 70% of small cell lung cancer (SCLC) contain the c-kit receptor. In the present study, a c-kit analysis has been extended to non-small cell lung cancer (NSCLC). The expressions of p53, vascular endothelial growth factor (VEGF) and cd34, in addition to c-kit, were evaluated to investigate the correlations between these proteins and to determine their potential relationships with the clinicopathological data.

Materials and Methods

Paraffin-embedded tumor sections, obtained from 147 patients with NSCLC, were immunohistochemically investigated using anti-c-kit, anti-p53, anti-VEGF and anti-cd34 antibodies.

Results

c-kit was expressed in 40 (27%) of the tumors examined: 27% of the adenocarcinomas, 27% of the squamous cell carcinomas and 29% of the undifferentiated carcinomas. p53 and VEG F immunoreactivities were present in 107 (73%) and 110 (75%) carcinomas, respectively. Anti-cd34 was negative in all samples. No associations were established among these proteins. The c-kit, however, showed a strong correlation with the T factor: T1 (n=11), 0%; T2 (n=49), 16% and T3 (n=87), 37% (p=.006).

Conclusion

It is suggested that in NSCLC c-kit is expressed relatively frequently and may become a therapeutic target for the patients with inoperable or recurrent c-kit positive tumors. The alterations in p53 probably constitute an early event, whereas the activated c-kit may contribute to tumor progression.

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  • Clinical and Prognostic Significance of CD117 in Non-Small Cell Lung Cancer: A Systemic Meta-Analysis
    Ying Su, Ru Chen, Zhongcheng Han, Rong Xu, Lili Ma, Reyina Wufuli, Hongbo Liu, Fang Wang, Lei Ma, Rui Chen, Jiang Liu
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    Mi Zhang, Jing Liang, Shi-Kun Jiang, Ling Xu, Yan-Ling Wu, Annoor Awadasseid, Xiao-Yin Zhao, Xu-Qiong Xiong, Hiroshi Sugiyama, Wen Zhang
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    HUI XIAO, JUAN WANG, YANAN LIU, LI LI
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    Misun Park, Won Kyu Kim, Meiying Song, Minhee Park, Hyunki Kim, Hye Jin Nam, Sung Hee Baek, Hoguen Kim
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The Expressions of Cytokeratin 7 and 20 in Epithelial Tumors: A Survey of 91 Cases
Dong Hoon Kim, Jong Eun Joo, Eun Kyung Kim, Ho Jung Lee, Won Mi Lee
Cancer Res Treat. 2003;35(4):355-363.   Published online August 31, 2003
DOI: https://doi.org/10.4143/crt.2003.35.4.355
AbstractAbstract PDF
PURPOSE
This study was performed to determine the expressions of cytokeratin 7 and cytokeratin 20 in epithelial neoplasms, and to investigate their potential role in the differential diagnosis of carcinomas of various organs.
MATERIALS AND METHODS
We investigated 91 various cases of primary and metastatic cancers, using a panel of commercially available monoclonal antibodies against cytokeratins 7 and 20 (CK7 and CK20), by immunohistochemistryand an avidin-biotin immunoperoxidase technique. The specimens were formalin-fixed and paraffin- embedded, and examined using 4micrometer thick serial sections.
RESULTS
The expression of CK7 was seen in the majority of carcinoma cases, including transitional cell carcinomas (100%), pulmonary adenocarcinomas (100%), ovarian serous adenocarcinomas (100%), cholangiocarcinomas (70%), colonic adenocarcinomas (64.29%) and invasive ductal carcinomas (60%). The expression of CK20 was seen in the majority of colorectal carcinomas cases (85.72%), but was virtually absent in pulmonary adenocarcinomas (0%), uterine cervical carcinomas (0%), ovarian carcinomas (0%), prostatic adenocarcinomas (0%), adenocarcinomas of the gall bladder (0%) and cholangiocarcinomas (12.5%).
CONCLUSION
In the all cases investigated, either CK7 or CK20 immunophenotypes were conserved in the tumor cells of primary tumors and in those of the corresponding metastatic lesions. It is suggested that CK7/CK20 immunophenotyping, in metastatic carcinomas of an unknown origin, maybe useful in the determination of the primary site of the metastasis.

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  • Occult urothelial carcinoma with mediastinal metastasis: A case report
    Jingfan Zheng, Xintong Peng, Xiaoqing Li, Yuyu Chen, Xinyi Li, Ling Fu, Ao Li, Zhong Lu
    Oncology Letters.2024;[Epub]     CrossRef
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    Xiaoqi Lin, Qiuying Shi, Ximing J. Yang
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Evaluation of Her-2/neu in Breast Cancer: Comparison of Immunohistochemistry and Polymerase Chain Reaction
Mi Ja Lee, Ho Jong Jeon
Cancer Res Treat. 2003;35(2):96-101.   Published online April 30, 2003
DOI: https://doi.org/10.4143/crt.2003.35.2.96
AbstractAbstract PDF
PURPOSE
In breast cancer, Her-2/neu amplification/overexpression predicts a poor clinical outcome, and enhanced survival benefits have been reported with Her-2/neu targeted therapy. Currently, there are several methods for assessing the amplification/overexpression of Her-2/neu, each having advantages and disadvantages. The aim of this work was to establish a reproducible, sensitive and specific method of testing for Her-2/neu, which could be used in diagnostic pathology laboratories. MATERIALS AND METHODS: We compared the immunohistochemistry (IHC) detection of Her-2/neu overexpression, with differential polymerase chain reaction (PCR) to assess the gene amplification of the Her-2/ neu, in 163 cases of invasive ductal carcinoma of the breast using paraffin-embedded tissue. In addition, assessment of the appropriate cut off points was established. RESULTS: The overexpression of the Her-2/neu was detected in 39 (23.9%) cases, and its amplification in 37 (22.7%) cases. The methods were positive in 21.5% of cases and negative in 74.8%. There was a 96.3% concordance between the two methods. The sensitivity and specificity of IHC, compared with PCR, were 94.6 and 96.8%, respectively. CONCLUSION: We conclude that the automation of PCR-based Her-2/neu testing approaches is expected to play an increasing role in the future of Her-2/neu testing. Also, we have demonstrated that IHC is a sensitive and specific method for assessing Her-2/neu stati in breast cancer, compared to PCR. The current study indicates that moderate, or strong, complete membrane staining in> or =10% of tumor cells provides an appropriate cut off point compared with PCR.
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Expression of Cyclooxygenase-2 Protein in Gastric Carcinogenesis
Seoung Wan Chae, Jin Hee Sohn, Hyung Sik Shin, Young Euy Park
Cancer Res Treat. 2002;34(4):252-257.   Published online August 31, 2002
DOI: https://doi.org/10.4143/crt.2002.34.4.252
AbstractAbstract PDF
PURPOSE
The increased expression of cyclooxygenase (COX)-2 has been implicated in the development and progression of human cancers. We investigated COX-2 expression in normal, gastric adenomas and adenocarcinomas.
MATERIALS AND METHODS
COX-2 protein was assayed in gastrectomy and biopsy specimens, from 68 gastric adenocarcinomas, 40 gastric adenomas and 35 normal gastric tissues, by immunohistochemistry, and 32 specimens of normal and adenocarcinomas by western blot analysis. Correlation between COX-2 expression and various clinicopathological factors were studied in the gastric adenocarcinoma.
RESULTS
COX-2 protein expression in epithelial cells was increased in 6/40 (15%) of the adenomas and 55/68 (80.9 %) of the adenocarcinomas, while normal mucosa was not expressed. COX-2 expression was increased in differ-entiated gastric carcinomas compared with those in the undifferentiated group (p<0.05). The expression of COX-2 protein was unrelated to tumor size, depth of tumor invasion and the presence of lymphatic or vascular invasions. Western blot analysis showed the enhanced expression of the COX-2 protein (23 out of 32)(71%) in gastric carcinomas compared to that of normal gastric mucosal epithelium.
CONCLUSION
The above results indicated that the expression of COX-2 protein occurs in dysplastic epithelium and gastric carcinomas, which suggests COX-2 expression may contribute to tumor formation.

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