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

Abstract

METHODS.Immunohistochemical staining was performed on formalin fixed, parafShinshu University School of Medicine, Matsufin embedded tissue sections of normal squamous epithelia (30 cases), cervical moto, Japan.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 p53protein. 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.

Variations of mitotic index in normal and dysplastic squamous epithelium of the uterine cervix as a function of endometrial maturation

“…As outlined in Table 3, our cervical intraepithelial neoplasia 1 group did not show any phase-dependent variation in mitotic index that was markedly discordant with the other cervical intraepithelial neoplasia grades. Kanai et al, 23 in contrast, found that while ER was decreased in dysplastic epithelium, PR was increased. Thus, the precise mechanistic basis for this potential hormonal influence remains to be elucidated.…”

“…[20][21][22] Nonetheless, it has long been recognized that cervical squamous epithelial cells contain sex-steroid receptors and hence, their proliferation and differentiation are influenced, to some extent, by the menstrual cycle and/ or sex-steroid hormonal levels. [20][21][22][23][24][25][26][27][28] Most studies have localized ERs and progesterone receptors (PRs), at minimum, to the basal and parabasal cell layers of the normal ectocervix. [20][21][22][23][24][25][26][27][28] Data on a possible correlation between the localization and the extent of ERs and the menstrual cycle phase are less homogeneous.…”

“…[20][21][22][23][24][25][26][27][28] Most studies have localized ERs and progesterone receptors (PRs), at minimum, to the basal and parabasal cell layers of the normal ectocervix. [20][21][22][23][24][25][26][27][28] Data on a possible correlation between the localization and the extent of ERs and the menstrual cycle phase are less homogeneous. Kanai et al 23 and Ciocca et al 22 both reported that the expression and localization of steroid hormone receptors did not vary significantly with the phase of the menstrual cycle.…”

“…[20][21][22][23][24][25][26][27][28] Data on a possible correlation between the localization and the extent of ERs and the menstrual cycle phase are less homogeneous. Kanai et al 23 and Ciocca et al 22 both reported that the expression and localization of steroid hormone receptors did not vary significantly with the phase of the menstrual cycle. In contrast, Scharl et al 21 found that the intraepithelial ER localization in the proliferative phase, in postmenopausal cervices and in early gestation, were in the basal, parabasal and intermediate cells, whereas in the secretory phase, ER staining was confined to the basal and parabasal cells.…”

“…The somewhat conflicting findings of the aforementioned studies notwithstanding, it can be stated that at minimum, the cervical epithelium appears to be under some degree of hormonal influence. [20][21][22][23][24][25][26][27][28] In the present retrospective analysis, we sought to explore the potential inter-relationships of these two factors-hormonal effects on the ectocervical epithelium and intraepithelial proliferative activity. Hormonal factors that significantly affect the mitotic index of normal epithelium may also theoretically influence the mitotic index of dysplastic epithelium.…”