Clinical and genetic characteristics of MSI-high versus MSS gastric cancer patients: A single-institution experience.

Abstract

e16091 Background: Microsatellite instability-high (MSI-H) gastric cancers (GC) are unique in genotype and have shown to achieve better clinical outcomes compared to microsatellite stable (MSS) GC. However, the distinct clinicopathologic features of MSI-H/MSS associated with genetic mutations remain poorly established outside of clinical trials. Our study aims to characterize the real-world clinicopathological and genetic characteristics of patients with MSI-H versus MSS GC. Methods: A single institution retrospective study was performed at City of Hope (COH) of 155 patients with reported MSI-H and MSS gastrointestinal cancers. Baseline characteristics were recorded including age, ethnicity, histology, stage, and overall survivals (OS). Next-generation sequencing (NGS) analysis was available for 35 samples with confirmed MSI-H/MSS GC. A two-sided Fisher’s exact test was performed to compare mutation frequencies between each group (MSI-H vs. MSS). Results: Clinically, patients with MSI-H GC were older with a median age of 67 years versus 64.5 years for MSS and more common for poorly differentiated adenocarcinoma. MSI-H tumors were more common for TMB-high (71%) compared to MSS (0%). MSI-H GC tumors showed greater PD-L1 positivity (100%) compared to MSS (0%), however, neither MSI-H nor MSS were positive for HER2 (0%). Among the top 36 mutated genes, patients with MSI-H showed a higher number of mutated genes per patient compared with patients with MSS (9.5 vs. 3.5).The most common mutated genes for patients with MSI-H were ARID1A (83%), RNF43 (50%), PIK3CA (42%), MSH3 (37%), TP53 (33%), MSH6 (33%), KMT2B (33%), and ACVR2A (33%). Meanwhile, most common mutated genes for patients with MSS were ARID1A (54%), TP53 (54%), and CDH1 (36%). Conclusions: Our real-world retrospective study identified significantly different clinicopathologic and genetic features of MSI-H versus MSS GC. Compared to patients with MSS GC, those with MSI-H GC were characterized by higher tumor mutational burden and PD-L1 positivity, both shown to predict response to immunotherapy and achieve favorable clinical outcome. Our findings provide valuable insight regarding real-world clinicopathological and genetic differences between MSI-H and MSS GC and support individualized biomarker-driven treatment strategies.