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Comprehensive expression profiles of gastric cancer molecular subtypes by immunohistochemistry: implications for individualized therapy

Authors
 Hyo Song Kim  ;  Su-Jin Shin  ;  Seung-Hoon Beom  ;  Minkyu Jung  ;  Yoon Young Choi  ;  Taeil Son  ;  Hyoung-Il Kim  ;  Jae-Ho Cheong  ;  Woo Jin Hyung  ;  Sung Hoon Noh  ;  Hyunsoo Chung  ;  Jun Chul Park  ;  Sung Kwan Shin  ;  Sang Kil Lee  ;  Yong Chan Lee  ;  Woong Sub Koom  ;  Joon Seok Lim  ;  Hyun Cheol Chung  ;  Sun Young Rha  ;  Hyunki Kim 
Citation
 Oncotarget, Vol.7(28) : 44608-44620, 2016 
Journal Title
 Oncotarget 
Issue Date
2016
MeSH
Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism* ; Cohort Studies ; Epstein-Barr Virus Infections/drug therapy ; Epstein-Barr Virus Infections/metabolism* ; Epstein-Barr Virus Infections/virology ; Female ; Herpesvirus 4, Human/genetics ; Humans ; Immunohistochemistry/methods* ; In Situ Hybridization ; Male ; Middle Aged ; PTEN Phosphohydrolase/metabolism ; RNA, Viral/genetics ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/metabolism* ; Stomach Neoplasms/virology ; Tumor Suppressor Protein p53/metabolism ; Young Adult
Keywords
gastric cancer ; immunohistochemistry ; in-situ hybridization ; molecular subtypes
Abstract
Gastric cancer (GC) is a leading cause of death. We aim to establish a clinically relevant assay that encompasses recent molecular classifications and provides useful clinical information in a large cohort of GC patients. A consecutive series of 438 GC patients that underwent palliative chemotherapy between 2014 and 2015 were assessed using 10 GC panels: EBER in-situ hybridization, immunohistochemistry for mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), receptor tyrosine kinases (RTKs; HER2, EGFR, and MET), PTEN, and p53 protein. With a median of one aberration, 3.3 % of samples analyzed were Epstein-Barr virus (EBV)-positive; 4.8%, MMR-deficient. RTKs were overexpressed in 218 patients; EGFR was most commonly overexpressed (39.9%), followed by HER2 (13.5%) and MET (12.1%). Furthermore, 2.5 % and 10.7 % of cases had simultaneous overexpression of three and two RTKs, respectively. p53 overexpression/null tumors were identified in 259 patients (59.1%), and PTEN loss was identified in 89 patients (20.3%). EBV-positivity was mutually exclusive with MMR-deficiency, predominantly identified in male patients, and these tumors were undifferentiated with proximal location. p53 mutant type was significantly found predominantly in the EBV-negative (60.6% vs 14.3%, P=0.001) and HER2-positive (78.0% vs 56.2%, P=0.002) groups. We described a molecular spectrum of distinct GC subtypes using clinically applicable assay. This assay will provide a convenient screening tool and facilitate the development of targeted agents in clinical trials.
DOI
10.18632/oncotarget.10115
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
금웅섭(Koom, Woong Sub) ORCID logo https://orcid.org/0000-0002-9435-7750
김현기(Kim, Hyunki) ORCID logo https://orcid.org/0000-0003-2292-5584
김형일(Kim, Hyoung Il) ORCID logo https://orcid.org/0000-0002-6134-4523
김효송(Kim, Hyo Song) ORCID logo https://orcid.org/0000-0002-0625-9828
노성훈(Noh, Sung Hoon) ORCID logo https://orcid.org/0000-0003-4386-6886
라선영(Rha, Sun Young) ORCID logo https://orcid.org/0000-0002-2512-4531
박준철(Park, Jun Chul) ORCID logo https://orcid.org/0000-0001-8018-0010
범승훈(Beom, Seung Hoon) ORCID logo https://orcid.org/0000-0001-7036-3753
손태일(Son, Tae Il) ORCID logo https://orcid.org/0000-0002-0327-5224
신상준(Shin, Sang Joon) ORCID logo https://orcid.org/0000-0001-5350-7241
신성관(Shin, Sung Kwan)
이상길(Lee, Sang Kil) ORCID logo https://orcid.org/0000-0002-0721-0364
이용찬(Lee, Yong Chan)
임준석(Lim, Joon Seok) ORCID logo https://orcid.org/0000-0002-0334-5042
정민규(Jung, Min Kyu) ORCID logo https://orcid.org/0000-0001-8281-3387
정재호(Cheong, Jae Ho) ORCID logo https://orcid.org/0000-0002-1703-1781
정현수(Chung, Hyun Soo)
정현철(Chung, Hyun Cheol) ORCID logo https://orcid.org/0000-0002-0920-9471
최윤영(Choi, Yoon Young) ORCID logo https://orcid.org/0000-0002-2179-7851
형우진(Hyung, Woo Jin) ORCID logo https://orcid.org/0000-0002-8593-9214
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/151703
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