DIFFERENTIAL EXPRESSION OF BCL-2 AND BAX IN SQUAMOUS-CELL CARCINOMAS OF THE ORAL CAVITY

The bcl-2 oncogene is a member of a family of genes encoding for prote ins which regulate apoptosis (programmed cell death). Recent evidence suggests that the bcl-2 protein is regulated by a homologous protein b ar which counteracts its effects and promotes apoptosis. Overexpressio n of bcl-2 has been reported in a number of human cancers, although co rrelations with tumour differentiation and clinical outcome are confli cting and depend on tumour type and site. We studied bcl-2 and bar pro tein expression in adjacent serial sections of 30 squamous cell carcin omas of the oral cavity and correlated this with tumour differentiatio n. Examination of normal epithelium showed bcl-2 expression confined t o basal keratinocytes and dendritic cells. The bar immunostaining was seen throughout the thickness of the epithelium but was most intense i n 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 d ifferentiated carcinomas where 6/7 (86%) showed strong staining. By co ntrast, bar immunoreactivity was strongest in the well-differentiated carcinomas with 8/11 (72%) staining strongly. In the well-differentiat ed tumour islands, there was inverse topographic distribution of bcl-2 and bar, with both proteins showing a pattern that recapitulated norm al epithelium. Upregulation of bcl-2 protein was identified in dysplas tic epithelium adjacent to invasive tumour and in many cases there was reduced bar immunostaining. These results suggest that alterations of bcl-2 and bar may play a role in the development of squamous cell car cinoma. Furthermore, disturbances of protein expression in dysplastic epithelium suggest a role in the early stages of epithelial carcinogen esis. Copyright (C) 1996 Elsevier Science Ltd