Differential expression of bcl-2 and bax in squamous cell carcinomas of the oral cavity.

Abstract

The bcl-2 oncogene is a member of a family of genes encoding for proteins which regulate apoptosis (programmed cell death). Recent evidence suggests that the bcl-2 protein is regulated by a homologous protein bax which counteracts its effects and promotes apoptosis. Overexpression of bcl-2 has been reported in a number of human cancers, although correlations with tumour differentiation and clinical outcome are conflicting and depend on tumour type and site. We studied bcl-2 and bax protein expression in adjacent serial sections of 30 squamous cell carcinomas of the oral cavity and correlated this with tumour differentiation. Examination of normal epithelium showed bcl-2 expression confined to basal keratinocytes and dendritic cells. The bax immunostaining was seen throughout the thickness of the epithelium but was most intense in the suprabasal cells. Overall, moderate or marked immunostaining for bcl-2 was identified in 18/30 (60%) carcinomas and for bax in 19/30 (63%) tumours. The bcl-2 immunoreactivity was strongest in the poorly differentiated carcinomas where 6/7 (86%) showed strong staining. By contrast, bax immunoreactivity was strongest in the well-differentiated carcinomas with 8/11 (72%) staining strongly. In the well-differentiated tumour islands, there was inverse topographic distribution of bcl-2 and bax, with both proteins showing a pattern that recapitulated normal epithelium. Upregulation of bcl-2 protein was identified in dysplastic epithelium adjacent to invasive tumour and in many cases there was reduced bax immunostaining. These results suggest that alterations of bcl-2 and bax may play a role in the development of squamous cell carcinoma. Furthermore, disturbances of protein expression in dysplastic epithelium suggest a role in the early stages of epithelial carcinogenesis.