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p53 Gene Status as a Predictor of Tumor Response to Induction Chemotherapy of Patients With Locoregionally Advanced Squamous Cell Carcinomas of the Head and Neck

From the Service d’Oto-Rhino-Laryngologie et de Chirurgie de la Face et du Cou, Antenne de Biostatistiques, L’Institut National de la Santé et de la Recherche Médicale (INSERM) U444, Laboratoires de Génétique Moléculaire, d’Histologie et de Biologie Tumorale, and Central d’Anatomie et de Cytologie Pathologiques, Hôpital Tenon, Paris, France.

Address reprint requests to Pierre Fouret, MD, Service d’Anatomie Pathologique, Hôpital Tenon, 75970 Paris Cedex 20, France; email fouret{at}infobiogen.fr

PURPOSE: To determine whether p53 gene status predicts tumor responses to platinum- and fluorouracil-based induction chemotherapy in locoregionally advanced squamous cell carcinomas of the head and neck.

PATIENTS AND METHODS: Tumor responses of 105 patients were measured at the primary tumor site. Objective response and major response were defined by a 50% and 80% reduction in tumor size, respectively. All coding parts of p53 gene were directly sequenced. p53 expression in tumor cells was determined by immunohistochemistry. Human papillomavirus infection was detected by polymerase chain reaction. Odd ratios were adjusted by stepwise logistic regression analysis.

RESULTS: p53 mutations, p53 expression, and tumor stage were sufficient to explain the variation in tumor responses to chemotherapy in multivariate models. p53 mutation was the only variable to significantly predict objective response (odds ratio, 0.23; 95% confidence interval, 0.10 to 0.57; P = .002) and was the strongest predictor of major response (odds ratio, 0.29; 95% confidence interval, 0.11 to 0.74; P = .006). p53 expression (odds ratio, 0.39; 95% confidence interval, 0.16 to 0.98) and tumor stage (odds ratio, 0.31; 95% confidence interval, 0.10 to 0.96) also predicted major response. Specific mutations (contact mutations) accounted for much of the reduction in the risk of major response associated with overall mutations. In complementary analyses, p53 expression was weakly predictive of major response in the subgroup with wild-type p53, and p53 mutations also predicted histologic response.

CONCLUSION: p53 gene mutations are strongly associated with a poor risk of both objective and major responses to chemotherapy. Contact mutations are associated with the lowest risk of major response to chemotherapy.

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