Enami Kaneko

MLH1 promoter hypermethylation predicts poorer prognosis in mismatch repair deficiency endometrial carcinomas

The antitumor effects of anti-PD-1 antibody against mismatch repair deficiency (MMR-D)-associated cancers have been reported. MMR-D is found in approximately 20%-30% of endometrial carcinomas (ECs) and frequently occurs due to Immunohistochemistry of MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed on specimens from 527 ECs treated at our university hospital from 2003 to 2018. Accordingly, 419 (79.5%), 65 (12.3%), and 43 (8.2%) cases were categorized as "MMR-proficient," "suspected-LS," and "met-EC," respectively. Significantly, "met-EC" had a lower proportion of grade 1 tumors (37.5%) and a higher proportion of stage III/IV tumors (37.2%) than the other groups. The overall and progression-free survival of "met-EC" were significantly worse than those of "suspected-LS" in all cases. In ECs with MMR-D, "met-ECs" were a subgroup with a poorer prognosis than "suspected-LS." "Met-ECs" would be the main target for anti-PD-1 antibody treatment, and its clinical susceptibility should be verified individually.