BCL-2 VS P53 PROTEIN EXPRESSION AND APOPTOTIC RATE IN HUMAN NONMELANOMA SKIN CANCERS

Background: A failure in the apoptotic response after severe genomic d amage could facilitate cell transformation and tumor development, and a constitutive overexpression of either p53 or bcl-2 protein in nonapo ptotic tumor cells could signify a defective bar-mediated apoptosis. O bjectives: To investigate whether a negative correlation occurs betwee n these 2 proteins in nonmelanoma skin cancer and whether overexpressi on of either protein is associated with a low rate of spontaneous apop tosis. Design: Immunohistochemical study of nonmelanoma skin cancer ar chive material.Setting: University referral center. Patients: White pa tients with tumors on sun-exposed skin areas (ie, 17 basal cell carcin omas and 22 squamous cell carcinomas). Main Outcome Measures: Positivi ty for p53 and bcl-2 were scored semiquantitatively on 4 levels, and t he percentages of apoptotic cells were determined. Results: A signific ant negative correlation between p53 and bcl-2 expression was found in the basal cell carcinomas, but not in the squamous cell carcinomas, l argely attributable to the low level of bcl-2 staining in the squamous cell carcinomas. Squamous cell carcinomas have a significantly higher number of apoptotic cells than basal cell carcinomas: 1.1% vs 0.6%, r espectively. This spontaneous apoptosis decreases with increasing bcl- 2 (in basal cell carcinoma), whereas it does not appear to be related to p53 level expression. Conclusions: These results indicate that a di sturbance in either p53 or bcl-2 suffices to enhance skin tumor format ion by suppressing apoptosis; bcl-2 appears to reduce the rate of spon taneous apoptosis, but an aberrant p53 expression does not, and this f actor may solely affect the apoptosis from exogenous genotoxicity.