Oncotarget

Research Papers:

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

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 and Hyunki Kim _

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Oncotarget. 2016; 7:44608-44620. https://doi.org/10.18632/oncotarget.10115

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Abstract

Hyo Song Kim1, Su-Jin Shin2, Seung-Hoon Beom1, Minkyu Jung1, Yoon Young Choi3, Taeil Son3, Hyoung-Il Kim3, Jae-Ho Cheong3, Woo Jin Hyung3, Sung Hoon Noh3, Hyunsoo Chung4, Jun Chul Park4, Sung Kwan Shin4, Sang Kil Lee4, Yong Chan Lee4, Woong Sub Koom5, Joon Seok Lim6, Hyun Cheol Chung1, Sun Young Rha1, Hyunki Kim2

1Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea

2Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea

3Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea

4Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea

5Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea

6Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea

Correspondence to:

Hyunki Kim, email: kimhyunki@yuhs.ac

Sun Young Rha, email: rha7655@yuhs.ac

Keywords: gastric cancer, molecular subtypes, immunohistochemistry, in-situ hybridization

Received: April 04, 2016    Accepted: May 29, 2016    Published: June 16, 2016

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.


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