p53, Rb, and cyclin D1 expression in human oral verrucous carcinomas

BACKGROUND. The verrucous carcinoma (VC), a tumor with low grade malignancy, appears to be associated with tobacco and human papillomavirus. The pathobiology of these tumors has not been extensively studied, and molecular genetic alterations have not been reported. In this study we investigated by immunohistochemistry the expression of p53, Rb, and cyclin D1 in a series of well-defined oral VC. Changes in the expression of these genes have been commonly reported in a variety of human tumors. METHODS. We studied 29 cases of VC, fixed in formalin and embedded in paraffin. Immunohistochemistry was carried out using the avidin-biotin immunoperoxidase technique. Polyclonal antibody CM-1 was used for p53, a rabbit polyclonal human RE antibody, Rb-WL-1 antibody for Rb and a rabbit polyclonal human cyclin D antibody for cyclin D1. RESULTS. Positive p53 expression (protein accumulation) was detected in 15 of the 29 VC analyzed. In some cases, p53-positive areas were small foci but in most of the cases extensive positive areas were observed. None of the cases studied showed alterations of Rb protein. The expression of cyclin D1 was determined in 18 cases of VC. Positive nuclear immunostaining was seen in 11 cases. CONCLUSIONS. p53 protein accumulation is frequently observed in these tumors suggesting possible mutations of this gene in VC. Overexpression of cyclin D1 but no alterations of Rb staining were also observed in this low grade tumor suggesting that Rb may be functionally inactivated by overexpression of cyclin D1 or HPV infection.