Immunohistochemical detection of sex steroid receptors, cyclins, and cyclin-dependent kinases in the normal and neoplastic squamous epithelia of the uterine cervix.

BACKGROUND

Malignant transformation of sex steroid-dependent tissues has been reported to be associated with abnormal expression of sex steroid receptors. In addition, abnormalities of cell cycle-related molecules have been demonstrated in various malignancies. However, expression of steroid receptors and cell cycle-related molecules in the process of malignant transformation of the ectocervical squamous epithelium, which also is a sex steroid-dependent tissue, has not been elucidated fully.

METHODS

Immunohistochemical staining was performed on formalin fixed, paraffin embedded tissue sections of normal squamous epithelia (30 cases), cervical intraepithelial neoplasia (CIN) (21 cases), and invasive squamous carcinoma (SCC) (33 cases), using antibodies against estrogen receptors (ER), progesterone receptors (PR), cyclins (E, A, and B1), cyclin-dependent kinases (cdk2 and cdc2), and p53 protein. In addition, growth activity of SCC was evaluated by Ki-67 labeling.

RESULTS

In the normal epithelia, diffuse proportionate to regional expression of ER/PR and sporadic expression of cyclins/cdks were observed mainly in the parabasal cells irrespective of the menstrual cycle. In the neoplastic lesions, the expression of ER markedly decreased; however, the expression of PR increased. The expression of cyclins, cdks, and p53 was increased in a considerable number of these neoplastic cases. In addition, cyclin A positive SCC had elevated Ki-67 labeling, whereas cyclin E positive SCC cases had lower Ki-67 labeling.

CONCLUSIONS

These findings suggest that malignant transformation of ectocervical epithelia is associated with loss of normal growth control by steroid hormones as well as with the acquisition of abnormal cell cycle regulatory mechanisms.