BCL-2-related apoptosis markers in cutaneous human papillomavirus-associated lesions

Background: Human papilloma virus (HPV) is an etiological agent in benign and malignant epithelial tumors. Resistance to apoptotic stimuli by viral strategies represents an immunologic escape mechanism during virus-induced tumor development and is critical for efficient replication of the virus. Objective: The aim of the present study was to investigate a role of bcl-family proteins in the anti-apoptotic pathways modulated by low-risk HPVs in the development of benign HPV-associated cutaneous tumors. Methods: Forty lesional biopsy specimens from HPV-associated cutaneous lesions and 11 non-lesional control skin biopsies were studied by immunohistochemical analysis for the differential expressions of HPV antigens, the pro-apoptotic bax protein, and the antiapoptotic bcl-2 and bcl-x proteins. Results: Compared with the normal epidermis, bcl-2 and bcl-x expression were significantly reduced in the lesional epidermis. Bax was expressed in HPV-associated cutaneous lesions, although the expression did not reveal a significant deviation from that in normal skin. Conclusion: These findings indicate a discordant expression of bcl2/ bcl-x and bax proteins in HPV-associated skin lesions and suggest that low-risk HPVs mediate other pathways that bypass the action of anti-apoptotic bcl-2 and bcl-x proteins. The presence of bax expression with a prominent decrease in bcl-2/ bax ratio and the lack of massive apoptosis in HPV-associated benign epithelial lesions may imply that interference with the pro-apoptotic proteins of bcl-family may constitute one of the several mechanisms mediated by HPV oncoproteins for the suppression of apoptotic process.