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Patterns of p53 Gene Mutations in Head and Neck Cancer: Full-Length Gene Sequencing and Results of Primary Radiotherapy¹

Faculty of Dentistry, University of Toronto, Toronto [M. E. S., R. C. K. J.]; Visible Genetics Inc., Toronto, Ontario [M. E. S., R. S.]; Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario [R. M., E. F., R. G., R. C. K. J.]; and Departments of Dentistry [R. C. K. J.] and Laboratory Medicine [R. C. K. J.], Sunnybrook and Women’s College Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada

p53 gene alterations are common in head and neck cancers, but their prognostic value has not been clearly established. Despite evidence in other cancers that sequencing of the entire p53 coding region provides prognostic information, 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 pretreatment biopsies from patients with laryngeal carcinomas by full-length gene sequencing and by immunohistochemistry (IHC). Associations among p53 genotype, protein expression, and local recurrence were assessed in 35 irradiated patients followed for a minimum of 5 years. DNA was extracted from formalin-fixed, paraffin-embedded biopsies, and exons 2–11 of the p53 gene were individually amplified by PCR and then directly sequenced. IHC was performed to detect mutant and wild-type p53 protein using the DO7 monoclonal antibody. p21 protein expression was assessed using the EA1 monoclonal antibody. Twenty genetic alterations were observed in 42 tumors (48%). Four of these alterations (20%) occurred outside exons 5–8. There was a significant association between p53 gene and protein status (² = 4.18, P = 0.04), although the correlation was weak ( coefficient = -0.327). Although local relapse following radiation was significantly associated with nodal status, no correlations were observed between p53 status (gene or IHC) and local recurrence 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 correlation between p53 status and local control suggests that this marker is not as powerful as traditional prognostic factors, such as lymph node status.

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