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, Hyunki Kim

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21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)44608-44620
Number of pages13
JournalOncotarget
Volume7
Issue number28
DOIs
Publication statusPublished - 2016 Jan 1

All Science Journal Classification (ASJC) codes

  • Oncology

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    Kim, H. S., Shin, S. J., Beom, S. H., Jung, M., Choi, Y. Y., Son, T., Kim, H. I., Cheong, J. H., Hyung, W. J., Noh, S. H., Chung, H., Park, J. C., Shin, S. K., Lee, S. K., Lee, Y. C., Koom, W. S., Lim, J. S., Chung, H. C., Rha, S. Y., & Kim, H. (2016). Comprehensive expression profiles of gastric cancer molecular subtypes by immunohistochemistry: Implications for individualized therapy. Oncotarget, 7(28), 44608-44620. https://doi.org/10.18632/oncotarget.10115