Expression of estrogen receptors, progesterone receptors, and an estrogen receptor-associated protein in the human cervix during the menstrual cycle and menopause

Cano, Antonio; Serra, Vicente; Rivera, José; Monmeneu, Rosa; Marzo, Carmen

doi:10.1016/s0015-0282(16)54005-9

Cited by 32 publications

(25 citation statements)

References 13 publications

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“…During a menstrual cycle and menopause, varying levels of hormones are released throughout the body that can cause changes in the cervix, including softening, drying, or thinning. 28,29 Permanent field effects or malignancy-associated changes that result from the presence or prior history of disease may account for the significant effect of such differences on Raman spectra. 30,31 Accounting for hormonal levels and history of disease prior to disease classification resulted in sensitivity and specificity rates of >95%.…”

Section: Introductionmentioning

confidence: 99%

Sensitivity of Raman spectroscopy to normal patient variability

et al. 2011

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Abstract. Many groups have used Raman spectroscopy for diagnosing cervical dysplasia; however, there have been few studies looking at the effect of normal physiological variations on Raman spectra. We assess four patient variables that may affect normal Raman spectra: Race/ethnicity, body mass index (BMI), parity, and socioeconomic status. Raman spectra were acquired from a diverse population of 75 patients undergoing routine screening for cervical dysplasia. Classification of Raman spectra from patients with a normal cervix is performed using sparse multinomial logistic regression (SMLR) to determine if any of these variables has a significant effect. Results suggest that BMI and parity have the greatest impact, whereas race/ethnicity and socioeconomic status have a limited effect. Incorporating BMI and obstetric history into classification algorithms may increase sensitivity and specificity rates of disease classification using Raman spectroscopy. Studies are underway to assess the effect of these variables on disease. C©2011 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3646210

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Section: Introductionmentioning

confidence: 99%

Sensitivity of Raman spectroscopy to normal patient variability

et al. 2011

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“…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. Cano et al 24 reported that the cervical epithelial ER content decreases during the secretory phase, whereas Mosny et al 25 reported the opposite: the latter authors found that in the secretory phase, ER-positive cells may be found up to the most superficial layers, in contrast to the proliferative phase, where they are variably localized to the basal and parabasal layers. 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.…”

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confidence: 98%

“…[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.…”

mentioning

confidence: 99%

“…[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.…”

mentioning

confidence: 99%

“…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.…”

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confidence: 99%

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

Fadare

Liang

et al. 2007

Modern Pathology

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Cervical intraepithelial neoplasia is a premalignant (dysplastic) lesion that is characterized by abnormal cellular proliferation, maturation and nuclear atypia. The intraepithelial distribution, density, and nature (typical or atypical) of mitotic figures are routinely utilized diagnostic criteria to grade dysplasia and to distinguish highgrade dysplasia from potential histologic mimics such as transitional metaplasia, atrophy or immature squamous metaplasia. In this study, we evaluated the total mitotic indices of the cervical epithelia in hysterectomy specimens from patients with and without dysplastic lesions and investigated a possible relationship between mitotic index and hormonal status, using the endometrial maturation phase as a surrogate indicator of the latter. Two hundred seventy-four cervices from hysterectomy specimens (135 cases without dysplasia, 33, 35 and 71 cases with grades 1, 2 and 3 cervical intraepithelial neoplasia, respectively) were analyzed. A cervical mitotic index (total mitotic figures/10 high-power fields in the most proliferative area) was determined for each case. The endometrium in each case was classified into atrophic, early proliferative, late proliferative and secretory. For all three dysplasia grades, cases in the proliferative endometrium group always had a higher average mitotic index than those in the secretory and atrophic endometrium groups; this observation also held true for the benign cases. Furthermore, in all three dysplasia grades, the average mitotic index was always lowest in the atrophic endometrium group. Although the mitotic index showed expected patterns of increases with increasing dysplasia grades for most of the endometrial phases, this was not a universal finding. Notably, the average mitotic index for our cervical intraepithelial neoplasia 1 cases with late proliferative endometrium was higher than our cervical intraepithelial neoplasia 2 cases with secretory and atrophic endometrium. It is concluded that hormonal status, as reflected in endometrial maturation, can significantly affect the mitotic index of dysplastic squamous epithelium of the uterine cervix. Our findings confirm that the pathologic grading of dysplasia, especially in equivocal cases such as in metaplastic squamous epithelium, should not be solely dependent on the finding mitoses in the cervical squamous epithelium. The full composite of histopathologic features should form the basis for this determination. The ectocervical epithelium, as does squamous epithelium at other anatomic locations, continuously undergoes an organized program of maturation and differentiation from the basal to the superficial layers, with morphologic correlates of a progressive decrease in nuclear size, nuclear/cytoplasmic ratio and a progressive increase in nuclear chromatin density, cytoplasmic size and cytoplasmic glycogen of constituent cells.

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

Kanai

Shiozawa

et al. 1998

Cancer

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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.

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Expression of estrogen receptors, progesterone receptors, and an estrogen receptor-associated protein in the human cervix during the menstrual cycle and menopause

Cited by 32 publications

References 13 publications

Sensitivity of Raman spectroscopy to normal patient variability

Sensitivity of Raman spectroscopy to normal patient variability

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

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

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