STEPWISE ABNORMALITY OF SEX STEROID-HORMONE RECEPTORS, TUMOR-SUPPRESSOR GENE-PRODUCTS (P53 AND RB), AND CYCLIN E IN UTERINE ENDOMETRIOID CARCINOMA

BACKGROUND, In the normal cell cycle, the appropriate interaction of f actors such as tumor suppressor gene products (retinoblastoma suscepti bility [Rb], p53) and cyclins is essential. Abnormalities in the inter action of these factors may result in malignant transformation of the cell. Malignant transformation of the endometrium, which is believed t o be a sex steroid-dependent tumor, probably involves a process of unc oupling of these factors and sex steroid hormone receptors. This study is designed to test this hypothesis. METHODS, Fifty-six patients whos e pathology slides contained either normal or hyperplastic endometrium adjacent to endometrial carcinoma were selected. Immunohistochemical staining of serial paraffin sections was performed using antibodies to estrogen receptors (ER) and progesterone receptors (PR), p53, and Rb, as well as cyclin E. RESULTS, The normal and hyperplastic endometria adjacent to carcinoma showed positive staining for ER and PR and negat ive staining for p53. Of 56 carcinomas, 39 (69.6%) showed homogeneous positive staining for ER and PR and negative staining for p53, whereas the remaining 17 carcinomas (30.4%) contained varied distributions of ER- and PR-negative cells, and p53-positive cells (6 were negative or focally positive for ER/PR and diffusely-positive for p53, 4 were reg ionally positive for ER/PR and regionally-positive for p53, and 7 were diffusely positive for ER/PR and focally-positive for p53). The p53-p ositive cells corresponded to those that stained negatively for ER/PR. This topographic inverse relationship between ER/PR expression and p5 3 expression also correlated with the staining intensities. Furthermor e, the cells with weak or negative staining for p53 had a tendency to stain positively for Rb and weakly positive for cyclin E, whereas the cancer cells with definite positivity for p53 tended to stain either w eakly or negatively for Rb and definitely positive for cyclin E. The c ells showing diffusely positive for p53 were present significantly in clinical Stage III and pathologic Grade G3. CONCLUSIONS, In the develo pment of endometrial carcinoma, stepwise abnormalities of sex steroid receptors, tumor suppressor gene products, and cyclins apparently exis t, and may correlate with the progression of the malignant process. (C ) 1996 American Cancer Society.