Clinicopathologic Features and Prognostic Significance of Immunohistochemistry and In Situ Hybridization Based Molecular Classification in Gastric Carcinoma

<b>Background/Aim:</b> Gastric carcinoma (GC) is a highly heterogeneous disease with many subtypes that have different morphologic and molecular characteristics. In the current study, we analyzed immunohistochemical (IHC) and <i>in situ</i> hybridization (ISH) features of GCs and evaluated their association with prognosis and clinicopathological features. <b>Materials and Methods: </b>Three hundred cases analyzed by IHC and ISH for microsatellite stability, p53, e-cadherin, HER2, PD-L1 expression, and Epstein-Barr virus (EBV) status. Cases were classified into five subgroups based on expression profile. The relationships between subgroups, clinicopathological features, and survival were determined. <b> Results:</b> Ten (3.3&#37;) cases were classified as EBV^-associated, 45 (15&#37;) as microsatellite instable (MSI), 73 (24.3&#37;) as EBV^-/microsatellite-stable (MSS)/epithelial-mesenchymal-transformation (EMT)-like, 75 (25&#37;) as EBV^-/MSS/ non-EMT-like/p53^&#43;, and 97 (32.3&#37;) as EBV^-/MSS/non-EMT-like/p53^-. The MSI subtype had the best overall survival (OS). In contrast, the EBV-/MSS/EMT-like subtype had the poorest OS. The MSI subtype was also related with old age of the patient and antrum-corpus localized tumors, whereas the EBV^-/MSS/EMT-like was associated with young age, larger tumor size, and advanced stage presentation. PD-L1 positivity is highly correlated with MSI and EBV-associated subtypes. <b>Conclusion:</b> Our data demonstrated a link between IHC/ISH characteristics of GC and clinical outcomes. IHC/ISH based molecular classification may be helpful in predicting the survival.