Comparative p53 mutational analysis of multiple primary cancers of the upper aerodigestive tract.

ABSTRACT

BACKGROUND: Tumors arising in the upper aerodigestive tract (UAT) are often associated with predisposing factors that place the patient at risk for development of multiple synchronous or metachronous tumors. The aim of this study was to evaluate p53 as a susceptibility gene in UAT malignancy. METHODS: Seventeen patients with 41 separate primary tumors involving esophagus (n = 15), larynx (n = 14), pharynx (n = 6), lung (n = 2), mouth (n = 2), and tongue (n = 2) were analyzed for the presence and specific genotype of p53 point mutation. Immunohistochemical staining of p53 and topographic genotyping consisting of polymerase chain reaction amplification and direct sequencing of p53 exons to 5 to 8 were performed. RESULTS: Eleven tumors were metachronous (6 months to 11 years), and 11 were synchronous. We found p53 point mutations in 19 (46.3%) of 41 tumors in exons 8 (n = 11), 7 (n = 4), 5 (n = 3), and 6 (n = 1). Tumors possessed either wild-type p53 or a single type of point mutation. Metastases displayed the identical genotype of its primary tumor in all cases. Most importantly, p53 genotype was found to be completely discordant between separate primary tumors for the same patient. CONCLUSIONS: Complete discordance in p53 genotype between separate primary UAT cancers strongly indicates that p53 is not functioning as a susceptibility gene in this setting.