PD-L1 Expression In Lynch Syndrome-associated And Sporadic Colorectal Carcinomas:a Retrospective Single-center Study In Chinese Patients

Objective: Present study aimed to clarify the correlation between programmed cell death ligand-1(PD-L1)expression and histological characteristics,type of mismatch repair deficiency(dMMR)deletion,microsatellite instability(MSI)status and germline mutation of Lynch syndrome(LS)in colorectal cancer of Chinese population by immunohistochemistry of PD-L1 andMMR,and detection of MSI and NGS.Methods: The clinicopathological data of 2187 colorectal cancer patients were retrospectively collected.MSI and germline mutations were detected in 170 patients with dMMR(mismatch repair deficient),and the expression of PD-L1(clone 22C3)was evaluated in 133 patients.Results: Among 170 dMMR patients,146(85.9%)patients exhibited as MSI-H while46(27.1%)patients carrying pathogenic or likely pathogenic germline mutations were diagnosed as Lynch Syndrome.In 133 dMMR patients with PD-L1 assessment,25(18.8%)cases exhibited PD-L1 positive expression.PD-L1 positivity correlated with higher p TNM stage(P=0.040),poorer differentiation(P=0.007)and medullary morphology(P=0.032).There was no statistical significance between PD-L1 positivity andMMR-deficient pattern or MSI-H loci or germline genetic alterations(P=0.403,0.996,0.674,respectively)in colon-rectal carcinomas which all manifesting mismatch repair deficiency.There were significant differences between sporadic DMMR and Lynch syndrome-related CRC in patient age(P=0.007)and degree of tumor differentiation(P=0.003).Conclusion: PD-L1 expression carcinomas are more frequently advanced poorly differentiated CRCs.This study represents the first to characterize differences in PD-L1 expression between LS-associated and sporadic mutant colon-rectal carcinomas.