Microsatellite instability in gastric cancer is a predictor of a favorable prognosis

Abstract

Evaluation of the frequency of microsatellite instability in gastric adenocarcinomas in patients of the Russian Federation, determination of the relationship of microsatellite instability with clinical and morphological characteristics and the impact on the prognosis. We used samples of surgical material from 310 patients with a verified diagnosis of gastric cancer. The age of the patients ranged from 22 to 85 years (mean 63 years). The median follow-up of patients was 83 months. Each sample was immunohistochemically stained with antibodies to microsatellite instability markers MLH1, MSH2, MSH6, and PMS2. The results were compared with the main clinical and morphological characteristics of gastric cancer and data on patient survival. The frequency of detection of MMR-negative tumors in the Russian population is 8.1% of all patients with gastric cancer. It was found that patients with MMR-negative gastric carcinomas are older (mean age 69 years, p=0.008). In this group predominates distal localization of tumors, type 2 according to R. Bormann classification (p=0.010), tubular histological type (p=0.010), intestinal subtype according to P. Lauren classification (p=0.003). There were no significant differences between MMR-negative and MMR-positive tumors in terms of other clinical and morphological parameters (including the stage of the tumor process). The overall median survival of patients with MMR-negative tumors was 76%, which significantly (p=0.013) exceeds that in the group of MMR-positive tumors (36%). It was found that despite significant differences in survival, MMR-status is not an significant prognostic factor in gastric cancer (HR=0.983). The established differences in patient survival make it possible to distinguish a group of MMR-negative tumors into a separate pathogenetic subtype of gastric cancer (MSI subtype) based on immunohistochemical studies. This subtype occurs predominantly in elderly patients with tubular gastric adenocarcinomas and is characterized by a favorable prognosis.