Immunohistochemical evaluation of COX-2 expression in HPV-positive cervical squamous intraepithelial lesions

Cyclooxygenase 2 (COX-2) regulates the prostaglandins production and it seems to have a role in the onset and progression of different malignant tumors, being overexpressed in numerous human malignancies and premalignant conditions. Some cellular elements from chronic inflammatory processes, together with stromal cells may be involved in neoplastic transformation of proliferative stem cells and in the process of tumor invasion. Cervical carcinoma, as a commonly pattern of different tumors, can express COX-2 in association with glutathione-S-transferase isoenzymes and can be considered as possible molecular targets in antitumoral therapy. The purpose of this study was to evaluate the expression of cyclooxygenase (COX)-2 in cervical squamous intraepithelial lesions of low-grade (LSIL) and high-grade (HSIL), with morphologic evidence of HPV infection. Immunostains with COX-2 antibodies were performed on formalin-fixed and paraffin-embedded tissue sections from 20 cervical biopsies: 10 with LSIL histopathologic diagnosis and 10 with HSIL histopathologic diagnosis. All LSIL biopsies and four HSIL cases (equivalent to CIN2) presented also intermediate squamous cells, with pathognomonic morphology of HPV infection (koilocytes). The Allred immunohistochemical score for the intensity of staining and the percent of cells stained was assigned. The slides were scored by three independent pathologists and compared across histological categories. Regarding the intensity of cytoplasmic COX-2 immunostaining, a weaker expression was observed in specimens with LSIL and a stronger one in those diagnosed with HSIL, the highest score being noted in HSIL corresponding to CIN3 lesions. The increase of COX-2 expression in cervical cancer precursors certifies that COX-2 may have a role in the development and progression of cervical squamous intraepithelial lesions.