title: Estrogen receptor, progesterone receptor, and bcl-2 are markers with prognostic significance in CIN III.
abstract: 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.
authors.affiliation: Department of Gynecology, Portuguese Cancer Institute, Coimbra, Portugal. jafmoutinho@mail.telepac.pt
authors.forename: J A
authors.initials: JA
authors.lastname: Fonseca-Moutinho
authors.forename: E
authors.initials: E
authors.lastname: Cruz
authors.forename: L
authors.initials: L
authors.lastname: Carvalho
authors.forename: H J M
authors.initials: HJ
authors.lastname: Prazeres
authors.forename: M M P
authors.initials: MM
authors.lastname: de Lacerda
authors.forename: D P
authors.initials: DP
authors.lastname: da Silva
authors.forename: F
authors.initials: F
authors.lastname: Mota
authors.forename: C F
authors.initials: CF
authors.lastname: de Oliveira
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000032:analysis / Q000096:biosynthesis*; D011980:Receptors, Progesterone / Q000032:analysis / Q000096:biosynthesis*; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology*; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone