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 Osman, I. Articles by Pfister, D. G. Search for Related Content PubMed PubMed Citation Articles by Osman, I. Articles by Pfister, D. G. Social Bookmarking                            What's this?

Alteration of p53 Pathway in Squamous Cell Carcinoma of the Head and Neck: Impact on Treatment Outcome in Patients Treated With Larynx Preservation Intent

From the Departments of Medicine, Radiation Oncology, Surgery, Pathology, and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY.

Supported in part by the Overman Fund and the Garban Intercapital Fund.Address reprint requests to: David G. Pfister, MD, Memorial Sloan-Kettering Cancer Center, Box 188, 1275 York Ave, New York, NY 10021; email: pfisterd{at}mskcc.org

PURPOSE: To identify the role of p53 pathway alteration(s) as predictors of treatment outcome in patients with advanced, resectable, squamous cell carcinoma (SCC) of the larynx and pharynx treated with larynx preservation (LP) intent.

PATIENTS AND METHODS: Seventy-one patients treated on two consecutive LP protocols were studied based on availability of representative tissues. We analyzed the expression pattern of p53, its upstream regulator mdm2, and downstream transcriptional target p21/WAF1 by immunohistochemistry. Positive phenotype was defined as 20% of tumor cells showing nuclear immunoreactivity. Results were correlated with treatment outcomes.

RESULTS: Positive phenotype was observed in 35 (49%) of 71 cases for p53, in 52 (74%) of 70 for mdm2, and in 37 (54%) of 68 for p21. There was no correlation between p53 phenotype and p21 nuclear accumulation. The mdm2-negative phenotype was most predictive of major response at the primary tumor site (P = .088). p53-positive phenotype was associated with worse local control with LP (LCLP; 49% v 23%, P = .053) and inferior overall survival (OS; 51% v 29%, P = .017) at 5 years. On Cox regression analysis, p53-positive phenotype predicted inferior OS (P = .033) and showed a trend for worse LCLP (P = .102). When analyzed in a multivariate model as continuous variables, p53 showed a stronger correlation with inferior OS (P < .01), and mdm2 was associated with worse OS (P < .01).

CONCLUSION: Among the three markers studied, our data support p53 phenotype as the most informative predictor of unfavorable outcomes in the LP setting, and suggest a role for mdm2 phenotype that requires further exploration. Our analysis does not support a p53-dependent mechanism for p21 expression. Prospective and larger studies are necessary before integration of these molecular markers as part of molecular staging and predictors for organ preservation or other outcomes.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				B. Singh and D. G. Pfister Individualized Treatment Selection in Patients With Head and Neck Cancer: Do Molecular Markers Meet the Challenge? J. Clin. Oncol., July 1, 2008; 26(19): 3114 - 3116. [Full Text] [PDF]

				G. B. van den Broek, V. B. Wreesmann, M. W.M. van den Brekel, C. R.N. Rasch, A. J.M. Balm, and P. H. Rao Genetic Abnormalities Associated with Chemoradiation Resistance of Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., August 1, 2007; 13(15): 4386 - 4391. [Abstract] [Full Text] [PDF]

				I. Ganly, S. Talbot, D. Carlson, A. Viale, E. Maghami, I. Osman, E. Sherman, D. Pfister, S. Chuai, A. R. Shaha, et al. Identification of Angiogenesis/Metastases Genes Predicting Chemoradiotherapy Response in Patients With Laryngopharyngeal Carcinoma J. Clin. Oncol., April 10, 2007; 25(11): 1369 - 1376. [Abstract] [Full Text] [PDF]

				S. Etemad-Moghadam, F. Baghaee, F. Tirgary, P. Motahhary, M. Khalili, N. Eshghyar, M. Alaedini, and M. Eslami Expression of p21WAF in Salivary Gland Mucoepidermoid Carcinoma and Its Relation to Histologic Grade International Journal of Surgical Pathology, January 1, 2007; 15(1): 6 - 13. [Abstract] [PDF]

				F. Maluf, C Cordon-Cardo, D. Verbel, J. Satagopan, M. Boyle, H Herr, and D. Bajorin Assessing interactions between mdm-2, p53, and bcl-2 as prognostic variables in muscle-invasive bladder cancer treated with neo-adjuvant chemotherapy followed by locoregional surgical treatment Ann. Onc., November 1, 2006; 17(11): 1677 - 1686. [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]

				M. Rodriguez-Pinilla, J. L. Rodriguez-Peralto, R. Hitt, J. J. Sanchez, C. Ballestin, A. Diez, L. Sanchez-Verde, F. Alameda, and M. Sanchez-Cespedes Cyclin A as a Predictive Factor for Chemotherapy Response in Advanced Head and Neck Cancer Clin. Cancer Res., December 15, 2004; 10(24): 8486 - 8492. [Abstract] [Full Text] [PDF]

				D. L. Schwartz, J. Rajendran, B. Yueh, M. D. Coltrera, M. LeBlanc, J. Eary, and K. Krohn FDG-PET Prediction of Head and Neck Squamous Cell Cancer Outcomes Arch Otolaryngol Head Neck Surg, December 1, 2004; 130(12): 1361 - 1367. [Abstract] [Full Text] [PDF]

				D. Polsky, K. Melzer, C. Hazan, K. S. Panageas, K. Busam, M. Drobnjak, H. Kamino, J. G. Spira, A. W. Kopf, A. Houghton, et al. HDM2 Protein Overexpression and Prognosis in Primary Malignant Melanoma J Natl Cancer Inst, December 4, 2002; 94(23): 1803 - 1806. [Abstract] [Full Text] [PDF]