Clinicopathologic features and genetic alterations to endometrioid carcinoma of the uterus with villoglandular differentiation

Serous and endometrioid carcinomas differ dramatically in their clinical be havior; however, the specific significance of villoglandular (papillary) di fferentiation in endometrioid carcinoma has been studied rarely. We compare d the clinicopathologic features and genetic alterations in 28 villoglandul ar endometrioid carcinomas compared with 60 nonvilloglandular endometrioid carcinomas and 60 healthy women. The study revealed a slight increase in th e frequency of early-stage disease in villoglandular tumors compared with n onvilloglandular tumors. No differences were observed in the age at onset o r cellular grade. The oncogene and susceptibility gene analyses revealed a positive association of K-ras oncogene mutation and germline variants of th e cytochrome P-450 1A1 (CYP1A1) gene and an inverse association of the p53P IN3 variant with villoglandular carcinomas, whereas no differences were obs erved in the c-erbB2/neu oncogene amplification or the methylenetetrahydrof olate reductase germline variant. Finally, a positive association was found between CYP1A1 and methylenetetrahydrofolate reductase variants and the pr esence of papillar differentiation in the myometrial component. The results suggest that the villoglandular differentiation pattern arises without agg ressive clinicopathologic features in a genetic background of transforming and carcinogen-metabolism genes, characteristic of estrogen-related endomet rial tumors (type 1) not exhibiting an unfavorable prognosis.