Koji Horie

Prognostic and clinicopathological implications of mismatch-repair deficiency and MLH1 promoter methylation status in endometrial carcinoma

The prevalence of MSI-H and MLH1 promoter hypermethylation (MLH1-PHM) as well as Lynch syndrome in Japanese patients with endometrial cancer (EC) has not been fully revealed. There is also a recent report that the prognosis of MLH1-PHM is worse than MLH1 non-PHM in EC; however, no large-scale studies have been conducted in Japan. We investigated the prevalence of MSI-H, MLH1-PHM and Lynch syndrome in EC cases and characteristic and prognosis of them. The 677 patients who were pathologically diagnosed with EC at the Saitama Cancer Center Hospital between 2013 and 2023 were investigated in this study. The MSI and abnormal DNA methylation of the MLH1 promoter were tested in all cases. Patients with MSI-H EC or a family history provided informed consent and examined germline testing for Lynch syndrome. Among the 677 ECs, 170 (25.1%) were MSI-high (MSI-H), and 105 were involved MLH1 hypermethylation. Two of 13 Lynch syndrome cases had MLH1-PHM in ECs. The MSI-H group had more G3 histology, but had a favorable prognosis with 5-year PFS and OS compared with the MSS group. The group with MLH1-PHM have more patients with G1/2 histology and more advanced disease. There was no difference in prognosis between MLH1-PHM and non-PHM groups. This study provides information on the prevalence of MSI-H and MLH1-PHM in EC in Japan. Besides, the prognostic of the MSI-H group is better than that of the MSS group, but no differences were found between the MLH1-PHM and MLH1 non-PHM groups.

Diagnostic accuracy and prognostic factors of uterine serous carcinoma in Japanese women: a multi-center study

This multi-center retrospective study aimed to clarify the characteristics, diagnostic accuracy, treatment outcomes, and prognostic factors of uterine serous carcinoma (USC) in Japanese women. The medical records of 193 patients who were treated between 2006 and 2008 at 24 participating institutions in the Japanese Clinical Oncology Group were examined, and pathological slides of 188 patients were re-checked through central pathology review (CPR), hematoxylin-eosin staining, and immunohistochemistry. USC was confirmed in 144 of the 188 (76.6%) patients using CPR, and only 50% were correctly diagnosed preoperatively. Forty-three patients were diagnosed with non-serous carcinoma, whereas one patient had metastasis from another organ. The average age was 65.7 years, and 19% of patients had a history of other cancers. The incidence of stage III-IV disease was 52.8%, and lymph node metastasis was found in 28.5% of patients. Extrauterine spread and distant metastasis occurred in 39% and 14% of patients, respectively. The 2-year overall survival and progression-free survival (PFS) rates were 56% and 42%, respectively. The PFS of patients with stage I and II who underwent complete staging surgery was 92.3%, and that of those without lymph node dissection or omentectomy was 33.3%. Patients with USC had a significantly worse prognosis than 43 patients with non-serous carcinoma. USC in Japanese women has characteristics different from those of endometrioid carcinoma, worse prognosis, and is difficult to diagnose preoperatively. Complete surgical staging is necessary even for early-stage disease. Additionally, new adjuvant treatment strategies, including molecular targeted therapy, should be explored.