34P Validation of a new scoring system for molecular subtyping of gastric cancer

Abstract

Molecular classification of gastric cancer may potentially provide tailored treatment options by predicting survival outcomes and patients’ response to therapy. In our prior study by Setia et al. [Modern Patho 29.7 (2016): 772-784], we identified five groups of gastric cancers based on Epstein–Barr virus (EBV) positivity, microsatellite instability (MSI), aberrant E-cadherin, and p53 expression (normal/aberrant). The aim of this study was to validate the association between these molecular subtypes and the prognosis of patients with gastric cancer from Romania. The molecular classification was reproduced in a retrospective cohort of 121 resected gastric cancers at Fundeni Clinical Institute, Bucharest. EBER in situ hybridization, p53, microsatellite instability, and E-cadherin expression were analyzed using immunohistochemical, RT-PCR and in situ hybridization techniques. EBV-positive gastric cancers represented 30% of the cases (n=36); microsatellite instable adenocarcinoma constituted 9% of the cases (n=11); aberrant expression of E-cadherin was identified in 17% (n=20) while aberrant p53 expression was noted in 34% (n=42) of the gastric cancers. The remaining patients with normal p53 expression represent 10% (n=12) of total cases. The MSI high subtype was associated with a significantly more favorable prognosis while gastric cancers with aberrant E-cadherin expression had the least favorable prognosis (log-rank, p=0.001). Patients with EBV cancer subtype had superior median overall survival compared to those with aberrant E-cadherin expression (p=0.04). The proposed molecular classification successfully stratified patients by survival. Our results demonstrated a trend for superior survival in the MSIhigh subtype and EBV-positive gastric adenocarcinomas. These data warrant further validation of this scoring system and the role of anti-tumor immunity in MSI-high and EBV-positive subtypes.