title: Comparative study of the expression of cellular cycle proteins in cervical intraepithelial lesions.
abstract: Interaction of human papilloma virus oncoproteins E6 and E7 with cell cycle proteins leads to disturbances of the cell cycle mechanism and subsequent alteration in the expression of some proteins, such as p16INK4a, cyclin D1, p53 and KI67. In this study, we compared alterations in the expression of these proteins during several stages of intraepithelial cervical carcinogenesis. Accordingly, an immunohistochemical study was performed on 50 cervical biopsies, including negative cases and intraepithelial neoplasias. The expression patterns of these markers were correlated with the histopathological diagnosis and infection with HPV. The p16INK4a, followed by Ki67, showed better correlation with cancer progression than p53 and cyclin D1, which recommends their use in the evaluation of cervical carcinogenesis. These monoclonal antibodies can be applied to cervical biopsy specimens to identify lesions transformed by oncogenic HPV, separating CIN 1 (p16INK4a positive) and identifying high-grade lesions by an increase in the cellular proliferation index (Ki67). In this way, we propose immunomarkers that can be applied in clinical practice to separate patients who need a conservative therapeutic approach from those who require a more aggressive treatment.
authors.affiliation: Department of Gynecology and Obstetrics, Department of Pathology, Medical School, Federal University of Bahia, Salvador, Bahia, Brazil. cmpq@globo.com
authors.forename: Conceição
authors.initials: C
authors.lastname: Queiroz
authors.forename: Tânia Correia
authors.initials: TC
authors.lastname: Silva
authors.forename: Venâncio A F
authors.initials: VA
authors.lastname: Alves
authors.forename: Luisa L
authors.initials: LL
authors.lastname: Villa
authors.forename: Maria Cecília
authors.initials: MC
authors.lastname: Costa
authors.forename: Ana Gabriela
authors.initials: AG
authors.lastname: Travassos
authors.forename: José Bouzas Araújo
authors.initials: JB
authors.lastname: Filho
authors.forename: Eduardo
authors.initials: E
authors.lastname: Studart
authors.forename: Tatiana
authors.initials: T
authors.lastname: Cheto
authors.forename: Luiz Antonio R
authors.initials: LA
authors.lastname: de Freitas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D002584:Cervix Uteri / Q000033:anatomy & histology / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1