Localization of an estrogen-responsive protein in the human cervix during menstrual cycle, pregnancy, and menopause and in abnormal cervical epithelia without atypia.

The presence and distribution of an estrogen-responsive protein with a molecular weight of 28,000 were investigated in the human cervix with use of a monoclonal antibody. This biochemical marker protein was localized with a light microscope and by immunocytochemical studies of the different cell types and cell layers of the cervix. The study involved 60 patients, 48 of whom were sexually active, eight pregnant, and four in menopause; strips of endometrial tissue were analyzed in 22 patients. In cycling women the estrogen-responsive protein was identified in the subcolumnar cells of the endocervix, whereas in the ectocervix the protein was detected mainly in the parabasal and intermediate cell layers but alternating with unstained areas. There were no significant variations in the presence of the protein in the ectocervical and endocervical epithelium during the different phases of the menstrual cycle. During pregnancy a more intense and homogeneous immunostaining of the protein was seen in the ectocervix, endocervical areas with squamous metaplasia showed strong estrogen-responsive immunostaining, and predecidual and decidual cells were positive for the protein. There were no prominent changes in the presence and distribution of the protein in the abnormal ectocervical samples without atypia. However, in the endocervix the protein detection was useful to follow the evolution of the subcolumnar cells to simple squamous metaplasia. These samples displayed intense estrogen-responsive immunostaining. No immunoreaction was observed in the cervix of menopausal women. The results of the present study have shown that the response of the normal uterine cervix to estrogenic influence is heterogeneous in different cervical cell types and in different sites within the same cell layer; during the normal menstrual cycle the capability of response of the cervical cells to variations of estrogen levels is limited when compared with the endometrium; and during pregnancy and in the process of indirect squamous metaplasia some of the cervical cells seem to be very reactive to estrogenic stimulation. This study defines the normal baseline for further analysis of the estrogen-regulated protein in the uterine cervix during abnormal growth.