Microsatellite Instability and P53 Aberrant Expression in Gastric Adenocarcinoma: Immunohistochemical Assessment and Correlation with Clinico-pathological Characteristics

Abstract

Background: Gastric cancer (GC) is among the five most frequent cancer worldwide, following lung, breast, colorectal, and prostate cancer. It is the 12th most prevalent cancer in both sexes in Egypt, accounting for 1.6% of all malignancies. Distinct molecular subtypes of gastric adenocarcinoma (e.g., microsatellite instable subtype and P53 aberrant subtype) have been reported by different classification systems. However, the relation of these molecular subtypes to different clinicopathological features is still controversial. Aim of the Work: To utilize the immunohistochemical expression of DNA MMR proteins (MLH1 and MSH2) and p53 to detect microsatellite unstable and P53 aberrant molecular types in gastric adenocarcinoma. Moreover, to correlate immunohistochemically detected microsatellite unstable and P53 aberrant molecular types of gastric carcinoma with different clinicopathological characteristics. Materials and Methods: The immunohistochemical expression of MLH1, MSH2 and P53 proteins was evaluated in 70 cases of gastric adenocarcinoma. Results: Microsatellite status/Mismatch repair status showed a statistically significant relation with WHO classification, tumor differentiation, lymph node status, and TNM staging. P53 aberrant type showed a statistically significant relation with tumor differentiation, depth of tumor invasion, lymph node status, and TNM staging. Conclusions and Recommendations: Microsatellite instable GC and P53 aberrant GC are two distinct molecular subtypes of gastric adenocarcinoma with distinct clinicopathological features and different prognostic outcomes. Microsatellite instable tumors are associated with good prognostic parameters while, P53 aberrant tumors are associated with poor prognostic parameters. Both subtypes could be detected using immunohistochemistry and could represent potential targets for future therapeutic agents.