Patterns of p53 gene mutations in head and neck cancer: Full-length gene sequencing and results of primary radiotherapy

p53 gene alterations are common in head and neck cancers, but their prognos tic value has not been clearly established. Despite evidence in other cance rs that sequencing of the entire p53 coding region provides prognostic info rmation, full-length p53 gene sequencing has rarely been performed in head and neck cancers. In this study, p53 was assessed in a series of 42 pretrea tment biopsies from patients with laryngeal carcinomas by full-length gene sequencing and by immunohistochemistry (IHC), Associations among p53 genoty pe, protein expression, and local recurrence were assessed in 35 irradiated patients followed for a minimum of 5 years. DNA was extracted from formali n-fixed, paraffin-embedded biopsies, and exons 2-11 of the p53 gene were in dividually amplified by PCR and then directly sequenced. IHC was performed to detect mutant and wild-type p53 protein using the DO7 monoclonal antibod y. p21 protein expression was assessed using the EA1 monoclonal antibody. T wenty genetic alterations were observed in 42 tumors (48%), Four of these a lterations (20%) occurred outside exons 5-8. There was a significant associ ation between p53 gene and protein status (chi(2) = 4.18, P = 0.04), althou gh the correlation was weak (phi coefficient = -0.327), Although local rela pse following radiation was significantly associated with nodal status, no correlations were observed between p53 status (gene or IHC) and local recur rence following radiation therapy, based on the Kaplan-Meier method. These results show that p53 mutations are common in laryngeal carcinomas and that a proportion occur outside traditionally examined regions. The lack of cor relation between p53 status and local control suggests that this marker is not as powerful as traditional prognostic factors, such as lymph node statu s.