Estrogen receptor, progesterone receptor, and bcl-2 are markers with prognostic significance in CIN III

Abstract

Abstract. Fonseca-Moutinho JA, Cruz E, Carvalho L, Prazeres HJM, de Lacerda MMP, da Silva DP, Mota F, de Oliveira CF. Estrogen receptor, progesterone receptor, and bcl-2 are markers with prognostic significance in CIN III. Int J Gynecol Cancer 2004;14:911-920.There are no known biological markers or technologies to predict the natural history of an individual CIN III. The probability of progression is considered greater with the persistence of high-risk human papillomavirus (HPV) infection and age. p53 polymorphism has been associated with cervical carcinogenesis. Hormone-induced cervical cancer is mediated by estrogen receptor (ER) and progesterone receptor (PR). In cervical cancer, increased bcl-2 and Bax immunoreactivity is generally associated with a better prognosis. The purpose of this study was to evaluate the value of HPV 16 and HPV 18 typing and p53 codon polymorphism genotyping by polymerase chain reaction and ER, PR, bcl-2, and Bax expression by immunohistochemistry in predicting the CIN III clinical behavior of CIN III lesions. We studied the expression of these prognostic factors in the CIN III adjacent to squamous cell microinvasive carcinomas of the cervix (MIC) from 29 patients with FIGO stage IA1 cervical cancer and in 25 patients with CIN III and no documented focus of invasion. In the MIC group, only the CIN III was considered at least 2 mm away from the microinvasive complex. The ER, PR, bcl-2, and Bax immunoreactivity was scored as positive (>10% staining cells) and negative (<10% staining cells). No significant difference was observed between MIC and CIN III group concerning HPV infection and p53 polymorphism. The ER, PR, bcl-2, and Bax immunohistochemical expression was stronger and more frequent in the CIN III group. After multivariable analysis, coexpression of ER, PR, and bcl-2 was the only independent factor in defining low risk of progression for CIN III. Our study suggests that coexpression of ER, PR, and bcl-2 may be a useful tool in identifying the CIN III lesions with low risk of progression to cervical cancer.KEYWORDS: cervical microinvasive carcinoma, CIN III, immunohistochemistry, prognosis.Cervical cancer is one of the most frequent cancers in women, with an estimated worldwide incidence of about 371,000 new cases per year and an overall 5-year survival ranging from 44 to 66% for all clinical stages (1) .

The Indicators of Predicting Disease Outcome in HPV Carcinogenesis

“…These data confirm the observations of Fonseca-Moutinho et al, (2004), that Bcl2 is an independent factor in defining low risk of progression for CIN 3 and co-expression of estrogen receptor, progesterone receptor, and Bcl2 may be a useful tool in identifying the CIN 3 lesions with low risk of progression toward cervical cancer. Bcl2 has a more important value in cancer, the ratio of Bcl2 to Bax expression determining the survival or the death following an apoptotic stimulus.…”

Co-Expression of p53 and Bcl-2 Proteins in Human Papillomavirus-Induced Premalignant Lesions of the Uterine Cervix: Correlation with Progression to Malignancy

“…Increased Bcl-2 protein expression appears to be associated with cervical carcinogenesis [40] . In several studies, Bcl-2 expression was increased in early [32,41] as well as advanced stages [8,42] of cervical lesions. In our study, Bcl-2 expression gradually increased from LSIL to HSIL with a statistical significance ( table 2 ), suggesting an association between Bcl-2 expression with stages of cervical dysplasia.…”

Balance of apoptotic and anti-apoptotic marker and perforin granule release in squamous intraepithelial lesions. HIV infection leads to a decrease in perforin degranulation

“…In the same way, Spinillo et al (2004) showed an increase of Bcl-2 expression correlated with the severity of CIN. Fonseca-Moutinho et al (2004) observed that estrogen receptor (ER) and progesterone receptor (PR), Bcl-2, and Bax immunohistochemical expression was stronger and more frequent in the CIN III group. After a multivariable analysis, coexpression of ER, PR, and Bcl-2 was the only independent factor in defining low risk of progression for CIN III.…”