Involvements of Estrogen Receptor,Proliferating Cell Nuclear Antigen and p53 in Endometrial Adenocarcinoma Development in Donryu Rats

Involvements of estrogen receptor (ER)α, proliferating cell nuclear antigen (PCNA) and p53in the uterine carcinogenesis process in Donryu rats, a high yield strain of the uterine cancerwere investigated immunohistochemically. ERα was expressed in atypical endometrial hyperplasia,accepted as a precancerous lesion of the uterine tumors, as well as well- and inmoderately-differentiated endometrial adenocarcinomas, and the intensities of expression weresimilar to those in the luminal epithelial cells of the atrophic uterus at 15 months of age.The expression, however, was negative in the tumor cells of poorly differentiated type. Goodgrowth of implanted grafts of the poorly-differentiated adenocarcinomas in both sexes with orwithout gonadectomy supported the estrogen independency of tumor progression to malignancy.PCNA labeling indices were increased with tumor development from atypical hyperplasia toadenocarcinoma. The tumor cells in poorly-differentiated adenocarcinomas were positive for p53positive but negative for p21 expression, suggesting accumulation of mutated p53. These resultsindicate that the consistent ERα expression is involved in initiation and promotion steps ofuterine carcinogenesis, but not progression. In addition, PCNA is related to tumor developmentand the expression of mutated p53 might be a late event during endometrial carcinogenesis.