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      저자 : Enami Kaneko (검색결과 1 건)
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        MLH1 promoter hypermethylation predicts poorer prognosis in mismatch repair deficiency endometrial carcinomas

        Enami Kaneko,Naoki Sato,Tae Sugawara,Aya Noto,Kazue Takahashi,Kenichi Makino,Yukihiro Terada 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.6

        Objective: The antitumor effects of anti-PD-1 antibody against mismatch repair deficiency (MMR-D)-associated cancers have been reported. MMR-D is found in approximately20%–30% of endometrial carcinomas (ECs) and frequently occurs due to promoter hypermethylation ( -PHM). ECs with -PHM are classified according to the molecular screening of Lynch syndrome (LS), but few detailed reports are available. The purpose of this study was to clarify the clinical features of EC with -PHM. Methods: 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. methylation analysis was added to cases with MLH1/PMS2 loss. ECs were classified as follows: cases that retained MMR proteins as “MMR-proficient;” cases with MLH1/PMS2 loss and -PHM as “met-EC;” and cases with other MMR protein loss and MLH1/PMS2 loss without -PHM as “suspected-LS.” The clinical features, including long-term prognosis, of each group, were analyzed. Results: 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. Conclusion: 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.

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