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

Abstract

Involvements of estrogen receptor (ER)α, proliferating cell nuclear antigen (PCNA) and p53 in the uterine carcinogenesis process in Donryu rats, a high yield strain of the uterine cancer were investigated immunohistochemically. ERα was expressed in atypical endometrial hyperplasia, accepted as a precancerous lesion of the uterine tumors, as well as well- and in moderately-differentiated endometrial adenocarcinomas, and the intensities of expression were similar 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. Good growth of implanted grafts of the poorly-differentiated adenocarcinomas in both sexes with or without gonadectomy supported the estrogen independency of tumor progression to malignancy. PCNA labeling indices were increased with tumor development from atypical hyperplasia to adenocarcinoma. The tumor cells in poorly-differentiated adenocarcinomas were positive for p53 positive but negative for p21 expression, suggesting accumulation of mutated p53. These results indicate that the consistent ERα expression is involved in initiation and promotion steps of uterine carcinogenesis, but not progression. In addition, PCNA is related to tumor development and the expression of mutated p53 might be a late event during endometrial carcinogenesis.

Keywords: ERα; Endometrial adenocarcinoma Donryu; PCNA; p53; rat.

Fig. 1.

Immunohistochemical expression profiles of ERα, PCNA and p53 and HE staining in representative areas of normal uteri (at 12 to 15 months of age) and various neoplastic lesions in the uteri. Well-diff., well-differentiated adenocarcinoma; Poorly-diff., poorly-differentiated adenocarcinomas.

Fig. 2.

Percentages of immunohistochemically positive cells for ERα, PCNA and p53 in representative areas of normal uteri (at 15 months of age) and various neoplastic lesions in the uteri. *P<0.05 and **P<0.01 indicate significant differences in the expression of endometrial epithelium (normal) and uterine proliferative lesions compared with that in normal aged rats at 5% and 1%, respectively. The column and bar are represent the mean and SD, respectively.

Fig. 3.

Growth curves of tumor grafts after implantation. OVX, ovariectomy.