The Impact of MSI Phenotype by MLH1 Expression in Gastric Adenocarcinomas: Critical Analysis of the Brazilian Experience

BACKGROUND: Gastric cancer remains a clinical concern due to its high prevalence and mortality; consequently, efforts for comprehensive molecular subtyping, as related to morphology and prognosis, are mandatory. MATERIALS AND METHODS: We correlated the immunohistochemical expression profile of a panel with two major mismatch-repair (MMR) enzymes MLH1 and MSH2 with clinicopathological features and prognosis in a series of 133 gastric cancers and compared with worldwide experience. RESULTS: MMR negativity was found associated to clinicopathological features as proximal location, predominantly polypoid and fungating macroscopic types (Bormann´s type I and II), intestinal and tubular morphology according to Lauren´s and WHO systems respectively, expansible type according to Ming classification, heavy lymphoplasmacytic infiltrate and absent perineural infiltration. Loss of MLH1 immunoexpression was related to a beneficial impact on disease-specific survival; an independent prognostic impact at multivariate models was observed in cases with the loss of MLH1. CONCLUSIONS: Taken together, these results validate the biological significance of immunohistochemical detection of MMR enzymes as a method to identify specific pathological features and to assess prognosis in gastric cancer.