Comprehensive expression profiles of gastric cancer molecular subtypes by immunohistochemistry: implications for individualized therapy
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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
Hyunki Kim, email: firstname.lastname@example.org
Sun Young Rha, email: email@example.com
Keywords: gastric cancer, molecular subtypes, immunohistochemistry, in-situ hybridization
Received: April 04, 2016 Accepted: May 29, 2016 Published: June 16, 2016
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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