title: p16 INK4a and Ki67 expression in normal, dysplastic and neoplastic uterine cervical epithelium and human papillomavirus (HPV) infection.
abstract: Cellular cycle proteins like the p16(INK4a) and the Ki67 proliferation nuclear antigen have been used as oncogenicity cellular markers. The E6 and E7 oncoproteins interact with tumor suppressor genes p53 and pRb, culminating with the p16(INK4a) overexpression. The objective of this study was to evaluate the presence of HPV-DNA in 174 cervical biopsies and correlate the different histological grades with the p16(INK4a) and Ki67 immunohistochemical expression (IHC). A cross-sectional study that enrolled a total of 174 women who underwent uterine cervical biopsies between February 2003 and December 2006, in southern Brazil, was performed. Cervical smear samples were analyzed for the presence of HPV-DNA through polymerase chain reaction (PCR), and biopsy samples were examined for p16(INK4A) and Ki67 expression through IHC techniques. The presence of HPV-DNA was observed in 89% of the tested patients, among which 52% were positive for high-risk (HR) viral types [16, 18 and 31]. Regarding p16(INK4a), an expression of 69% was observed, being expressed in 100% of the high-grade squamous lesions (HSIL) and HR-HPV-DNA positives. Ki67 expression was associated with the lesion grade, being more expressive in the most severe lesions (p<0.001). p16(INK4A) and Ki67 markers coexpression was present in 86% of the samples (p<0.001), being 100% among those positive to HR-HPV-DNA with HSIL (p<0.001). The results suggest an association between the presence of HR-HPV infection and the p16(INK4a) and Ki67 expression and which is even stronger among women with HSIL.
authors.affiliation: Post Graduate Programs in Medical Sciences and Epidemiology, Federal University of Rio Grande do Sul, Brazil; School of Pharmacy, Federal University of Rio Grande do Sul, Brazil. Electronic address: luciane1011@gmail.com.
authors.forename: L N
authors.initials: LN
authors.lastname: Calil
authors.affiliation: Post Graduate Programs in Medical Sciences and Epidemiology, Federal University of Rio Grande do Sul, Brazil; Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Brazil.
authors.forename: M I A
authors.initials: MI
authors.lastname: Edelweiss
authors.affiliation: Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Meurer
authors.affiliation: Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Brazil.
authors.forename: C N
authors.initials: CN
authors.lastname: Igansi
authors.affiliation: Post Graduate Programs in Medical Sciences and Epidemiology, Federal University of Rio Grande do Sul, Brazil; Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Brazil.
authors.forename: M C
authors.initials: MC
authors.lastname: Bozzetti
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D002584:Cervix Uteri / Q000473:pathology* / Q000821:virology; D003430:Cross-Sectional Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen
keywords: Cervical cancer; HPV infection; Ki67; p16(INK4a)