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Oncotarget. 2016 Jul 12;7(28):44608-44620. doi: 10.18632/oncotarget.10115.

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

Author information

1
Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
2
Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.
3
Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
4
Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
5
Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea.
6
Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea.

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.

KEYWORDS:

gastric cancer; immunohistochemistry; in-situ hybridization; molecular subtypes

PMID:
27331626
PMCID:
PMC5190122
DOI:
10.18632/oncotarget.10115
[Indexed for MEDLINE]
Free PMC Article

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