P53 TUMOR-SUPPRESSOR GENE AND RAS ONCOGENE MUTATIONS IN HYPOPHARYNGEAL SQUAMOUS-CELL CARCINOMAS

To examine the potential role of p53 and ras gene mutations in hypopha ryngeal tumorigenesis, twenty-eight primary hypopharyngeal carcinomas, obtained at biopsy or total pharyngolaryngectomy, were investigated. Exons 5 through 9 of the p53 gene and exons 1 and 2 of the H-, K-, N-r as gene were screened using a combination of immunohistochemistry and single-strand conformation polymorphism analysis of polymerase chain r eaction products (PCR-SSCP). The targeted DNA sequences coding for p53 and ras were confirmed by direct DNA sequencing. Point mutations of p 53 were found in 9 (32.1%) of the 28 cases, including one with a doubl e mutation, 3 in exon 5, 1 in exon 6, 2 in exon 7 and 4 in exon 8. Pos itive nuclear immunostaining for p53 was evident in 14 (50.0%) lesions . Seven (25.0%) of the 28 demonstrated point mutations in the H-rns ge ne, and 11 (39.3%) showed positive cytoplasmic staining for I as. The 5-year survival rate was worse with than without p53 overexpression (p <0.05). The present results suggest that gene mutations, although the y occur at a relatively low incidence, are involved in hypopharyngeal tumorigenesis with p53 expression being a prognostic factor.