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

Kleber Simões, Carlos Eduardo Jacob, Rui Manuel Reis, Bruno Zilberstein, Suely Nonogaki, Rodrigo Albergaria Réssio, Alda Wakamatsu, Cláudio Bresciani, Joaquim Jose Gama-Rodrigues, Ivan Cecconello, Adhemar Longatto-Filho, Venâncio Avancini Ferreira Alves


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.


Microsatellite instability; Mismatch repair enzymes; Gastric cancer; Pathology; Prognosis

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