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p53 Alterations Predict Tumor Response to Neoadjuvant Chemotherapy in Head and Neck Squamous Cell Carcinoma: A Prospective Series

From the Laboratoire de Toxicologie Moléculaire, L’Institut National de la Santé et de la Recherche Médicale; Génotoxicologie et Modulation de l’Expression Génique, Laboratoire d’Anatomo-Pathologie; Service d’Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale; Service de Chirurgie Générale Digestive et Oncologique Assistance Publique-Hopitaux de Paris, Université-Paris V, Paris, France.

Address reprint requests to Philippe Beaune, MD, Laboratoire de Toxicologie Moléculaire, L’Institut National de la Santé et de la Recherche Médicale, U490 Faculté de Médecine des Saints Pères, 45 Rue des Saints Pères, 75270 Paris, Cedex 06, France; email Pierre.Laurent-Puig{at}biomedicale.univ-paris5.fr

PURPOSE: The tumor suppressor gene p53 plays a crucial role in cell cycle control and apoptosis in response to DNA damages. p53 gene mutations and allelic losses at 17p are one of the most common genetic alterations in primary head and neck squamous cell carcinoma (HNSCC). Alterations of the p53 gene have been shown to contribute to carcinogenesis and drug resistance.

PATIENTS AND METHODS: In this prospective series, patients with HNSCC were treated with cisplatin-fluorouracil neoadjuvant chemotherapy. p53 status was characterized in 106 patients with HNSCC (p53 mutations, allelic losses at p53 locus, and plasma anti-p53 antibodies) to determine the existence of a relationship between p53 gene status and response to neoadjuvant chemotherapy.

RESULTS: Exons 4 to 9 of the p53 gene were analyzed, and mutations were found in 72 of 106 patients with HNSCC. p53 mutations were associated with loss of heterozygosity at chromosome 17p (P < .001). The prevalence of p53-mutated tumors was higher in the group of patients with nonresponse to neoadjuvant chemotherapy than in the group of responders (81% v 61%, respectively; P < .04). When compiling p53 mutations and anti-p53 antibodies in plasma, the correlation between p53 status and response to chemotherapy was significant (87% v 57%, respectively; P = .003). A multivariate analysis showed that p53 status is an independent predictive factor of response to chemotherapy.

CONCLUSION: This prospective study suggests that p53 status may be a useful indicator of response to neoadjuvant chemotherapy in HNSCC.

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