Genotypic and phenotypic alterations of p53 in head and neck squamous-cell carcinoma

p53 is the most frequently altered suppressor gene in human cancers. The genotypic and corresponding phenotypic abnormalities of this gene in head and neck squamous cell carcinoma (HNSCC) remain undefined. We analyzed the loss of heterozygosity (LOH) by restriction fragment length polymorphism (RFLP) at three polymorphic loci in the p53 gene and performed immunohistochemistry (MC) for its protein on paraffin-embedded tumor tissue from 20 previously sequenced tumor specimens. LOH was noted at one or more of the three polymorphic sites within the p53 gene in 12 (67%) of the 18 informative samples. Concordance between LOH and mutations was observed in 14 (78%) cases. Twelve (60%) tumors with point mutations were immunohistochemically reactive to p53 antibody and two (10%) lacked both genetic and immunohistochemical alterations. In six tumors (30%) contradictory results between immunohistochemistry and molecular analysis were observed. Our data indicate that: (i) simultaneous deletion and mutation of both p53 alleles was observed in the majority of head and neck squamous carcinomas and implicate this gene in the oncogenesis of these neoplasms, (ii) p53 immunohistochemical analysis may not fully account for the different molecular alterations of this gene, and (iii) no correlation between p53 abnormalities and clinicopathologic or DNA content characteristics of HNSCC was found.