Prognostic significance of p53 gene mutations in laryngeal cancer

Objective/Hypothesis: We examined whether p53 gene mutations were predictive of clinical behavior in laryngeal cancer. Study Design: Retrospective study of 45 patients with laryngeal cancer from 1985 to 1997, Methods: DNA was extracted from tumor tissue and subject to polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) as well as DNA sequencing. The clinical outcome was correlated to the presence or absence of a p53 mutation. Results: The p53 gene was analyzed by direct DNA sequencing and was found to be mutated in 33% (15/45) of patients. The presence of a p53 mutation was associated with a significant improvement in overall survival (80% vs. 49%, P <.03) and a trend toward improved disease-free survival (87% vs, 60%, P =.08). When other prognostic factors were adjusted, multivariate analysis revealed a trend toward improvement in overall survival as well as disease-free survival. Conclusion: Depending on the location of a p53 mutation, the suppressive functions or clinical outcome may or may not be affected. Fifty-three percent of mutations were detected in nonconserved regions as opposed to 17% as reported in colon cancer. In colon cancer, mutations in conserved regions of the p53 gene predicted a poorer survival, whereas nonconserved gene mutations were not predictive. In our group of patients, p53 mutations predicted a better prognosis, which may be due to a large proportion of mutations that lie within nonconserved areas. The predictive power of p53 gene mutations may depend on functional loss and inactivation of highly conserved areas and must be tested in a prospective trial.