Immunohistochemical analysis of estrogen receptors, progesterone receptors, Ki-67 antigen, and human papillomavirus DNA in normal and neoplastic epithelium of the uterine cervix

Abstract

To investigate the relationship between the sex steroid receptor (estrogen receptor [ER] and progesterone receptor [PR]) status and the cell proliferation kinetics during the menstrual cycle in normal and neoplastic epithelium of the uterine cervix, immunohistochemical localization of ER, PR, and cell proliferation‐associated antigen, Ki‐67, was investigated in 35 normal cervical specimens, 3 condylomas, 26 cervical intraepithelial neoplasia (CIN) samples, and 22 invasive squamous carcinoma samples. The presence of human papillomavirus (HPV) DNA was also studied. In the normal cervix, basal cells were usually ER positive, PR negative, and Ki‐67 negative throughout the menstrual cycle. Parabasal cells were ER positive and PR negative in the follicular phase, but ER negative and PR positive, and Ki‐67 positive in the luteal phase, and Ki‐67‐positive cells increased in number in the luteal phase. In contrast, PR positivity was observed in the cells of condyloma (2 of 2 cases), CIN (19 of 26 cases), and invasive squamous carcinoma (13 of 22 cases) irrespective of the menstrual phase, Moreover, most neoplastic cells containing HPV DNA type 16/18 were ER negative, whereas several lesions containing HPV DNA type 31/33/35 were weakly ER positive. Many Ki‐67‐labeled cells were observed in the neoplastic lesions. These results suggest that reduced ER expression and increased PR expression are associated with the proliferation of normal cervical squamous epithelium, and this proliferation‐related receptor status, which is probably induced by HPV infection, is usually expressed in neoplastic cervical squamous cells.

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

“…[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.…”

“…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.…”

Panel of villin, pro-ex-c, estrogen receptor and progesterone receptor expressions could help in differentiation between endocervical and endometrioid adenocarcinoma

“…proliferation of normal cervical squamous epithelium, and this proliferation-related receptor status which is probably induced by HPV infection and is usually expressed in neoplastic cervical squamous cells (37). Socolov et al reported that well-differentiated EMC was ER-and PRpositive, so that ER-positive expression was significantly correlated with PR expression.…”

In Situ Hybridization, with or Without Tyramide Signal Amplification, in Evaluation of Human Papillomavirus Status Inearly Stage Cervical Carcinoma

“…The association of high-risk HPV types with malignant transformation of epithelial cells of the uterine cervix is now accepted [2][3][4][5][6][7][8][9]. Human papillomavirus type 16 is the most common high-risk HPV type [10-13], being detected in nearly half of all cervical carcinoma and cervical intraepithelial neoplasia (CIN) 2/3 lesions [14][15][16], and is followed by HPV type 18, which is detected in 14-25% of invasive cervical carcinomas [14,15].…”