p53 mutations and p53, WAF-1, Bax and Bcl-2 expression in field cancerization of the head and neck

Squamous cell carcinomas of the Head and Neck (SCCHN) ape related to carcin ogens and proceed through multiple genetic and morphological steps. The aim of this study was to establish the status of p53 gene and p53-regulated pr oteins (Bax, Bcl-2 and Waf-1) expression in head and neck simultaneous pren eoplastic and invasive lesions from patients with chronic alcohol and tobac co exposure. PCR-SSCP analysis of p53 gene and immunohistochemical analysis of Waf-1, Bm and Bcl-2 proteins were performed in 30 representative microd issected samples of mucosa exposed to carcinogens and preneoplastic or inva sive lesions from 8 patients. P53 mutations Mime detected in all steps of c arcinogenesis, but not in normal mucosa without carcinogen exposure. P53 mu tations, were different and multiple in concomittant areas of mucosa expose d to carcinogens preneoplastic and invasive lesions at distant locations. W af-1 and Bax protein expression was found in 100% of biopsies. Bcl-2 presen ted as basal cell positive staining in 95% of normal and preinvasive lesion s and was overexpressed in only 30% of tumors, independently of p53 gene st atus. Bax/Bcl-2 ratio was > 1 in all premalignant lesions and < 1 in tumor samples only There is evidence for the early, polyclonal origin of synchron ous multiple preneoplastic and neoplastic lesions in the cancerization fiel d. A P53 independant pathway seems to be implicated in Waf-1, Bax and Bcl-2 expression with an inversion of the Bax/Bcl-2 ratio restricted to invasive carcinomas.