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 approximately 20%–30% of endometrial carcinomas (ECs) and frequently occurs due to MLH1 promoter hypermethylation (MLH1-PHM). ECs with MLH1-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 MLH1-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. MLH1 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 MLH1-PHM as “met-EC;” and cases with other MMR protein loss and MLH1/PMS2 loss without MLH1-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.

A 66-year-old, postmenopausal woman was referred to our hospital because of abnormal breast cancer screening results. A tumor was found in the upper outer part of the left breast. Biopsy revealed papillotubular carcinoma, ER (Allred score total score [TS] 3 = proportion score [PS] 2 + intensity score [IS] 1), PgR (Allred score TS 3 = PS 2 + IS 1), HER2 (2+), fluorescent in situ hybridization 1.1 (negative), and Ki-67 labeling index 15%. In diagnostic imaging, the tumor size was 35 mm. The diagnosis was T2N0M0 Stage IIA, luminal B-like breast cancer. First, letrozole 2.5 mg/day was administered as preoperative hormone therapy. After 2 months of treatment with letrozole, the tumor size had increased to 44 mm and preoperative hormone therapy was discontinued. She was started on preoperative chemotherapy (4 courses of epirubicin plus cyclophsphamide followed by 4 courses of triweekly docetaxel). The tumor size decreased, becoming undetectable. After these preoperative treatments, nipple-sparing mastectomy, sentinel lymph node biopsy, and breast reconstruction with a primary latissimus dorsi flap were performed. As of 3 years and 6 months after the operation, there has been no recurrence. At first, preoperative hormone therapy is performed for Luminal B-like breast cancer as in this case, if the response is insufficient, preoperative chemotherapy after hormone therapy may be a therapeutic option.