This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cabelguenne, A. Articles by Laurent-Puig, P. Search for Related Content PubMed PubMed Citation Articles by Cabelguenne, A. Articles by Laurent-Puig, P.

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.

This article has been cited by other articles:

				E. M. Smith, D. Wang, L. M. Rubenstein, W. A. Morris, L. P. Turek, and T. H. Haugen Association between p53 and Human Papillomavirus in Head and Neck Cancer Survival Cancer Epidemiol. Biomarkers Prev., February 1, 2008; 17(2): 421 - 427. [Abstract] [Full Text] [PDF]

				S. Choi and J.N. Myers Molecular Pathogenesis of Oral Squamous Cell Carcinoma: Implications for Therapy J. Dent. Res., January 1, 2008; 87(1): 14 - 32. [Abstract] [Full Text] [PDF]

				J Peltonen, J A Welsh, and K H Vahakangas Is there a role for PCR-SSCP among the methods for missense mutation detection of TP53 gene? Human and Experimental Toxicology, January 1, 2007; 26(1): 9 - 18. [Abstract] [PDF]

				L. Licitra, F. Perrone, P. Bossi, S. Suardi, L. Mariani, R. Artusi, M. Oggionni, C. Rossini, G. Cantu, M. Squadrelli, et al. High-Risk Human Papillomavirus Affects Prognosis in Patients With Surgically Treated Oropharyngeal Squamous Cell Carcinoma J. Clin. Oncol., December 20, 2006; 24(36): 5630 - 5636. [Abstract] [Full Text] [PDF]

				F. Perrone, S. Suardi, E. Pastore, P. Casieri, M. Orsenigo, S. Caramuta, G. Dagrada, M. Losa, L. Licitra, P. Bossi, et al. Molecular and Cytogenetic Subgroups of Oropharyngeal Squamous Cell Carcinoma. Clin. Cancer Res., November 15, 2006; 12(22): 6643 - 6651. [Abstract] [Full Text] [PDF]

				D. G. Pfister, S. A. Laurie, G. S. Weinstein, W. M. Mendenhall, D. J. Adelstein, K. K. Ang, G. L. Clayman, S. G. Fisher, A. A. Forastiere, L. B. Harrison, et al. American Society of Clinical Oncology Clinical Practice Guideline for the Use of Larynx-Preservation Strategies in the Treatment of Laryngeal Cancer J. Clin. Oncol., August 1, 2006; 24(22): 3693 - 3704. [Abstract] [Full Text] [PDF]

				P Alhopuro, S K Ylisaukko-oja, W J Koskinen, P Bono, J Arola, H J Jarvinen, J-P Mecklin, T Atula, R Kontio, A A Makitie, et al. The MDM2 promoter polymorphism SNP309T->G and the risk of uterine leiomyosarcoma, colorectal cancer, and squamous cell carcinoma of the head and neck J. Med. Genet., September 1, 2005; 42(9): 694 - 698. [Abstract] [Full Text] [PDF]

				P. A. Kyzas, K. T. Loizou, and J. P. A. Ioannidis Selective Reporting Biases in Cancer Prognostic Factor Studies J Natl Cancer Inst, July 20, 2005; 97(14): 1043 - 1055. [Abstract] [Full Text] [PDF]

				F. Vikhanskaya, M. M. Siddique, M. Kei Lee, M. Broggini, and K. Sabapathy Evaluation of the Combined Effect of p53 Codon 72 Polymorphism and Hotspot Mutations in Response to Anticancer Drugs Clin. Cancer Res., June 15, 2005; 11(12): 4348 - 4356. [Abstract] [Full Text] [PDF]

				L. Licitra, S. Suardi, P. Bossi, L.D. Locati, L. Mariani, P. Quattrone, S. Lo Vullo, M. Oggionni, P. Olmi, G. Cantu, et al. Prediction of TP53 Status for Primary Cisplatin, Fluorouracil, and Leucovorin Chemotherapy in Ethmoid Sinus Intestinal-Type Adenocarcinoma J. Clin. Oncol., December 15, 2004; 22(24): 4901 - 4906. [Abstract] [Full Text] [PDF]

				J. C. Rhee, F. R. Khuri, and D. M. Shin Advances in Chemoprevention of Head and Neck Cancer Oncologist, June 1, 2004; 9(3): 302 - 311. [Abstract] [Full Text] [PDF]

				H. Blons, S. Gad, F. Zinzindohoue, I. Maniere, J. Beauregard, D. Tregouet, D. Brasnu, P. Beaune, O. Laccourreye, and P. Laurent-Puig Matrix Metalloproteinase 3 Polymorphism: A Predictive Factor of Response to Neoadjuvant Chemotherapy in Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., April 15, 2004; 10(8): 2594 - 2599. [Abstract] [Full Text] [PDF]

				L. Licitra and J. B. Vermorken Is there still a role for neoadjuvant chemotherapy in head and neck cancer? Ann. Onc., January 1, 2004; 15(1): 7 - 11. [Abstract] [Full Text] [PDF]

				S. Geisler, A.-L. Borresen-Dale, H. Johnsen, T. Aas, J. Geisler, L. A. Akslen, G. Anker, and P. E. Lonning TP53 Gene Mutations Predict the Response to Neoadjuvant Treatment with 5-Fluorouracil and Mitomycin in Locally Advanced Breast Cancer Clin. Cancer Res., November 15, 2003; 9(15): 5582 - 5588. [Abstract] [Full Text] [PDF]

				K. Ott, H. Vogelsang, J. Mueller, K. Becker, M. Muller, U. Fink, J. R. Siewert, H. Hofler, and G. Keller Chromosomal Instability Rather Than p53 Mutation Is Associated with Response to Neoadjuvant Cisplatin-based Chemotherapy in Gastric Carcinoma Clin. Cancer Res., June 1, 2003; 9(6): 2307 - 2315. [Abstract] [Full Text] [PDF]

				C. Monnerat, S. Faivre, S. Temam, J. Bourhis, and E. Raymond End points for new agents in induction chemotherapy for locally advanced head and neck cancers Ann. Onc., July 1, 2002; 13(7): 995 - 1006. [Abstract] [Full Text] [PDF]

				N. Tonisson, J. Zernant, A. Kurg, H. Pavel, G. Slavin, H. Roomere, A. Meiel, P. Hainaut, and A. Metspalu Evaluating the arrayed primer extension resequencing assay of TP53 tumor suppressor gene PNAS, April 16, 2002; 99(8): 5503 - 5508. [Abstract] [Full Text] [PDF]

				J.-C. Lin, K. Y. Chen, W.-Y. Wang, J.-S. Jan, W.-M. Liang, C.-S. Tsai, and Y.-H. Wei Detection of Epstein-Barr Virus DNA in the Peripheral-Blood Cells of Patients With Nasopharyngeal Carcinoma: Relationship to Distant Metastasis and Survival J. Clin. Oncol., May 15, 2001; 19(10): 2607 - 2615. [Abstract] [Full Text] [PDF]