Clinicopathological Features and Prognostic Value of Mismatch Repair Protein Deficiency in Gastric Cancer

The microsatellite instability (MSI) tumor is one of the four molecular subtypes in gastric cancer (GC). MSI tumors are sensitive to immune checkpoint blockade therapy. However the prevalence and characteristics of MSI in GCs remains unclear. We aimed to clarify relationships between MSI and clinicopathological features along with patients' survival rates. Data was collected from a cohort of 567 consecutive GC patients who received radical gastrectomy in Fudan University Shanghai Cancer Center. Expression of four DNA mismatch repair proteins (MMRPs)-MLH1, PSM2, MSH2, MSH6 was assessed using immunohistochemistry staining. Absence of any of the four MMRPs was defined as deficiency mismatch repair (dMMR). Tumors with preserved expression of all MMRPs were considered MMR-proficient (pMMR). Chi-squared test or Fisher's exact probability test was used to detect correlation between MMR status and clinicopathological parameters. Kaplan-Meier method and Log-rank test were used for survival analysis. Fifty-seven cases (57/567, 10.1%) were confirmed as dMMR. The dMMR status was in significant correlation with older age (<0.001), female gender (=0.016), distal tumor location in stomach (=0.002), intestinal Lauren classification (<0.001), less lymph node metastasis (=0.040), and less nerve invasion (=0.016). The dMMR tumors often exhibited unique nested, trabecular or solid growth pattern with an expanding margin and many infiltrating lymphocytes. Patients with dMMR phenotype had improved disease-free survival (=0.024) and overall survival rates (=0.025) compared to those with pMMR status. Cox regression analysis manifested dMMR status was an independent factor of better prognosis. In summary, GC with dMMR subtype had distinct clinicopathological features.