[High incidence of p53 mutations in primary and metastatic head and neck tumors. Frequent protein overexpression in normal epithelium]

Abstract

Mutation of the p53 tumor suppressor gene is the most commonly observed gene alteration in human cancers. In order to identify new prognostic factors and tumor aggressiveness in squamous cell head and neck carcinomas, we analyzed 50 node metastases and 28 primary tumors including 13 matched specimens for p53 alterations. Mutations were found in 54 (69%) tumors, 76% of which were missense, 9% were nonsense and 15% were microdeletions or microinsertions. Twenty-five mutations were transitions mostly G-->A (40%) and 20 were transversions mostly G-->T (25%) thus confirming the role of tobacco carcinogens in the induction of these mutations. For eight patients mutations were observed in matched primary tumors and metastases, indicating clonal dissemination of tumor cells in most of these carcinomas. Furthermore the incidence of mutations was not different in primary tumors and node metastases indicating that this gene alteration was not related to the metastatic dissemination. No correlation was found between mutation and clinical parameters, the 8-year survival rates were not different (log rank test: P = 0.49) in patients with and without mutation. There was a good correlation between p53 mutation and protein overexpression (Fisher's exact test: P < 10(-4). Interestingly, immunostaining was also observed in basal cells from normal mucosa and in early lesions adjacent to the primary tumor in 11/15 specimens irrespective of the presence of mutation in the corresponding tumors. p53 protein overexpression may therefore constitute a biomarker for early stages of carcinogenesis of the head and neck epithelium.