HIGH-INCIDENCE OF P53 MUTATIONS IN HEAD A ND NECK PRIMARY TUMORS AND METASTASES - FREQUENT P53 PROTEIN OVEREXPRESSION IN NORMAL EPITHELIUM

Mutation of the p53 tumor suppressor gene is the most commonly observe d gene alteration in human cancers. In order to identify new prognosti c factors and tumor aggressiveness in squamous cell head and neck carc inomas, 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% wer e microdeletions or microinsertions. Twenty-five mutations were transi tions mostly G --> A (40%) and 20 were transversions mostly G --> T (2 5%) thus confirming the role of tobacco carcinogens in the induction o f these mutations. For eight patients mutations were observed in match ed primary tumors and metastases, indicating clonal dissemination of t umor cells in most of these carcinomas. Furthermore the incidence of m utations was not different in primary tumors and node metastases indic ating that this gene alteration was not related to the metastatic diss emination. No correlation was found between mutation and clinical para meters, the g-year survival rates were not different (log rank test: P = 0.49) in patients with and without mutation. There was a good corre lation 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 p rimary tumor in 11/15 specimens irrespective of the presence of mutati on in the corresponding tumors. p53 protein overexpression may therefo re constitute a biomarker for early stages of carcinogenesis of the he ad and neck epithelium.