Comparative study of the expression of cellular cycle proteins in cervical intraepithelial lesions

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 p16(INK4a), cyclin DI, p53 and KI67. In this study, we compared alterations in the expression of these proteins during several stages of intra-epitelial 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 p16(INK4a), followed by Ki67, showed better correlation with cancer progression than p53 and cyclin DI, 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 (p16(INK4a) 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. (c) 2006 Elsevier GmbH. All rights reserved.