A novel case of endometrial dedifferentiated adenocarcinoma associated with MLH1 promotor hypermethylation and microsatellite instability

Abstract Endometrial dedifferentiated carcinoma is a rare, malignant tumor whose molecular alterations have not been clarified yet. We report a novel case of a 61-year old woman who presented with irregular vaginal bleeding after menopause and a 3 cm uterus mass. Histology revealed endometrial dedifferentiated adenocarcinoma, a rare subtype comprised of undifferentiated adenocarcinoma. The patient still survived 1 year after surgery without chemotherapy and radiotherapy. Immunohistochemistry revealed loss of MLH1/PMS2 expression and retained MSH2/MSH6 expression. Consistently, microsatellite instability was detected indicative of high microsatellite instability (MSI-H). No BRAF V600E, KRAS and POLE mutations were identified. Remarkably, the promoter regions of mutL homolog 1(MLH1) were methylated. Furthermore, several tumor cells were PD-L1 positive in this case with a concentration at the infiltrating tumor edge indicating MSI-H in endometrial dedifferentiated adenocarcinoma is a potential predictive factor for response to immunotherapy targeting the PD-1 or its ligand PD-L1.