title: Immunohistochemical expression of p16INK4a and bcl-2 according to HPV type and to the progression of cervical squamous intraepithelial lesions.
abstract: Inactivation of the cell cycle inhibitor gene p16MTS1 seems to be involved in human papillomavirus (HPV)-related carcinogenesis because E6 and E7 oncoproteins may impair p16INK4a and, indirectly, bcl-2 functions. In this study, we analyzed the role of immunohistochemical expression of p16INK4a and bcl-2 in HPV-infected cervical biopsies as prognostic markers of the progression of squamous intraepithelial lesion (SIL). Sixty-five cervical biopsies were stratified into two subgroups according to the second biopsy: 27 of them maintained a low-grade (LG)-SIL diagnosis, and 38 progressed from LG-SIL to high-grade (HG)-SIL. p16INK4a and bcl-2 quantitative expression levels were measured by the immunoperoxidase method. PCR-DNA techniques were used to detect and type HPV. The Wilcoxon and Fisher exact tests were employed for the statistical analysis. In the group with an LG-SIL diagnosis at the second biopsy, no significant associations were found between p16INK4a and bcl-2 expression and presence of HPV16/18. In the group that progressed to HG-SIL, a significant association was observed between p16INK4a overexpression and HPV16/18 presence (p=0.021), but none with bcl-2 levels. It is concluded that immunohistochemical bcl-2 expression may not be useful for predicting the progression of HPV-related SIL. In contrast, p16INK4a overexpression seemed to be associated with HPV 16 and 18, suggesting that it may be a good marker for predicting SIL progression.
authors.affiliation: Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil. epigin@uol.com.br
authors.forename: Márcia C M
authors.initials: MC
authors.lastname: Guimarães
authors.forename: Maria Alice G
authors.initials: MA
authors.lastname: Gonçalves
authors.forename: Christiane P
authors.initials: CP
authors.lastname: Soares
authors.forename: Jussara S R
authors.initials: JS
authors.lastname: Bettini
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Duarte
authors.forename: Edson G
authors.initials: EG
authors.lastname: Soares
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D027383:Papillomaviridae / Q000145:classification* / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000378:metabolism* / Q000821:virology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019253:Proto-Oncogene Proteins c-bcl-2