The heterogeneity between lynch-associated and sporadic mmr deficiency in colorectal cancers

Abstract

Background: Previous studies demonstrated that prognosis of germline deficiency in mismatch repair protein (dMMR) was different from that of sporadic dMMR. The underlying mechanism has not been studied. Methods: From a prospectively maintained database, we collected dMMR colorectal cancer (CRC) patients identified by postoperative immunohistochemistry screening. According to genetic test, patients were grouped as Lynch-associated or sporadic dMMR.We compared the clinical-pathological features, prognosis, and immunoreactive differences between the two groups. By whole-exome sequencing and neoantigen detection pipeline, mutational frequencies and neoantigen burdens were also compared. All statistical tests were two-sided. Results: Sixty-seven sporadic dMMR and 85 Lynch-associated CRC patients were included in the study. Sporadic dMMR patients were older (P < .001) and their tumors were poorly differentiated (P .03). The survival was better in the Lynch-associated group (P .001). After adjustment, the difference still remained statistically significant (hazard ratio 0.29, 95% confidence interval 0.09 to 0.95, P .04). The scores of Crohn's-like reaction (CRO; P