Mismatch repair deficiency is implicated in carcinoma arising from ovarian teratoma
Publication in refereed journal


摘要Malignant transformation of benign mature ovarian teratoma can result in a wide spectrum of cancer, including a variety of carcinoma, sarcoma, or melanoma. The role of mismatch repair defects in such malignant transformation is still elusive. In view of current immunotherapy, the role of mismatch repair deficiency can have significant implications on therapeutic strategy. Thus, we aimed to investigate the possible involvement of mismatch repair deficiency in somatic-type carcinoma arising from teratoma. We examined seven cases of malignant transformation of ovarian teratoma to carcinoma from the years 2000-2017. Mismatch repair deficiency was demonstrated in two cases, one of which was a squamous carcinoma and another a sebaceous carcinoma. By immunohistochemistry and molecular studies, we detected mismatch repair protein deficiency, microsatellite instability (MSI) and MLH1 promoter methylation in the derived carcinoma, but not in the benign teratoma, indicating mismatch repair deficiency was implicated in the process of malignant transformation. Our findings expand the spectrum of genetic alterations which are known to accompany malignant changes in benign teratoma. This finding is also of potential therapeutic significance, as mismatch repair deficient tumours can often be responsive to immune checkpoint blockade because of the high mutational load. In conclusion, we report that a subset of teratoma-derived carcinoma harbours MLH1 promoter methylation which underlies DNA mismatch repair deficiency, and this subset of patients has the potential to benefit from immunotherapy.
著者Cheung AHK, Chow C, Yu MY, Law WWT, Law PPY, Choi PCL, Kang W, To KF
頁次67 - 73
關鍵詞Teratoma, microsatellite instability, immunotherapy
Web of Science 學科類別Pathology;Pathology

上次更新時間 2020-05-08 於 04:40