p53 in endometrial cancer and its putative precursors: evidence for diverse pathways of tumorigenesis

Abstract

To elucidate the role of p53 abnormalities in endometrial tumorigenesis, a diverse group of endometrial neoplasms and their putative precursors, atypical endometrial hyperplasia, and endometrial intraepithelial carcinoma (EIC) were studied using a conventional immunohistochemical technique. Immunostaining for p53 protein was detected in 24 (86%) of 28 serous carcinomas compared with nine (20%) of 45 endometrioid carcinomas (P < .001). Immunoreactivity was also detected in two (100%) of two clear cell carcinomas, five (83%) of six mixed endometrioid/serous carcinomas, and seven (70%) of 10 malignant mixed mesodermal tumors. Benign endometrial tissue and 12 examples of atypical endometrial hyperplasia were nonreactive. In 27 (79%) of 34 tumors containing EIC, both the tumor and EIC were immunoreactive for p53, whereas in 7 (21%) both were negative. Immunostaining for p53 highlighted small foci of EIC and showed the extent and distribution of the lesions. The strong association and similar p53 immunostaining pattern of EIC and serous carcinoma support the hypothesis that serous carcinomas develop from endometrial surface epithelium that demonstrates abnormal p53 protein expression in conjunction with transformation to EIC. Mutation of p53 seems unrelated to the development of endometrioid carcinoma from atypical endometrial hyperplasia but may be related to dedifferentiation in some of these neoplasms.