bcl-2 vs p53 Protein expression and apoptotic rate in human nonmelanoma skin cancers

Background: A failure in the apoptotic response after severe genomic damage could facilitate cell transformation and tumor development, and a constitutive overexpression of either p53 or bcl-2 protein in nonapoptotic tumor cells could signify a defective bax-mediated apoptosis. Objectives: To investigate whether a negative correlation occurs between these 2 proteins in nonmelanoma skin cancer and whether overexpression of either protein is associated with a low rate of spontaneous apoptosis. Design: Immunohistochemical study of nonmelanoma skin cancer archive material. Setting: University referral center. Patients: White patients with tumors on sun-exposed skin areas (ie, 17 basal cell carcinomas and 22 squamous cell carcinomas). Main Outcome Measures: Positivity for p53 and bcl-2 were scored semiquantitatively on 4 levels, and the percentages of apoptotic cells were determined. Results: A significant negative correlation between p53 and bcl- 2 expression was found in the basal cell carcinomas, but not in the squamous cell carcinomas, largely 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%, respectively. 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 disturbance in either p53 or bcl-2 suffices to enhance skin tumor formation by suppressing apoptosis; bcl-2 appears to reduce the rate of spontaneous apoptosis, but an aberrant p53 expression does not, and this factor may solely affect the apoptosis from exogenous genotoxicity.