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Previous Volume 357:2552-2561 December 20, 2007 Number 25 Next

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ABSTRACT

Background The abrogation of function of the tumor-suppressor protein p53 as a result of mutation of its gene, TP53, is one of the most common genetic alterations in cancer cells. We evaluated TP53 mutations and survival in patients with squamous-cell carcinoma of the head and neck.

Methods A total of 560 patients with squamous-cell carcinoma of the head and neck who were treated surgically with curative intent were enrolled in our prospective multicenter, 7-year study. TP53 mutations were analyzed in DNA from the tumor specimens with the use of the Affymetrix p53 chip and the Surveyor DNA endonuclease and denaturing high-performance liquid chromatography. Mutations were classified into two groups, disruptive and nondisruptive, according to the degree of disturbance of protein structure predicted from the crystal structure of the p53–DNA complexes. TP53 mutational status was compared with clinical outcome.

Results TP53 mutations were found in tumors from 224 of 420 patients (53.3%). As compared with wild-type TP53, the presence of any TP53 mutation was associated with decreased overall survival (hazard ratio for death, 1.4; 95% confidence interval [CI], 1.1 to 1.8; P=0.009), with an even stronger association with disruptive mutations (hazard ratio, 1.7; 95% CI, 1.3 to 2.4; P<0.001) and no significant association with nondisruptive mutations (hazard ratio, 1.2; 95% CI, 0.9 to 1.7; P=0.16). In multivariate analyses a disruptive TP53 alteration, as compared with the absence of a TP53 mutation, had an independent, significant association with decreased survival (hazard ratio, 1.7; 95% CI, 1.2 to 2.4; P=0.003).

Conclusions Disruptive TP53 mutations in tumor DNA are associated with reduced survival after surgical treatment of squamous-cell carcinoma of the head and neck.

Source Information

From Johns Hopkins University (M.L.P., A.F., N.B., J.A.C., W.W., D.S., W.M.K.) and Greater Baltimore Medical Center (J.S.) — both in Baltimore; Center for Integrated Research, Laboratory of Molecular Medicine and Biotechnology, University Campus Bio-Medico of Rome, Rome (M.L.P.); Dana–Farber Cancer Institute, Boston (J.M., M.A.G.); Fox Chase Cancer Center, Philadelphia (J.A.R.); University of Miami–Sylvester Comprehensive Cancer Center, Miami (J.G.); and University of Kentucky, Lexington (D.K.).

Address reprint requests to Dr. Koch at the Department of Otolaryngology, Johns Hopkins University School of Medicine, 601 N. Caroline St., JHOC 6221, Baltimore, MD 21287, or at wkoch{at}jhmi.edu.

Full Text of this Article

Related Letters:

TP53 Mutations in Head and Neck Cancer
Beutner D., Klussmann J.-P., Guntinas-Lichius O., Perrone F., Bossi P., Licitra L., Koch W., Poeta M. L., Manola J.
Extract | Full Text | PDF  
N Engl J Med 2008; 358:1194-1195, Mar 13, 2008. Correspondence

This article has been cited by other articles:

• Beutner, D., Klussmann, J.-P., Guntinas-Lichius, O., Perrone, F., Bossi, P., Licitra, L., Koch, W., Poeta, M. L., Manola, J. (2008). TP53 mutations in head and neck cancer.. NEJM 358: 1194-1195 [Full Text]  
• Westra, W. H., Taube, J. M., Poeta, M.L., Begum, S., Sidransky, D., Koch, W. M. (2008). Inverse Relationship between Human Papillomavirus-16 Infection and Disruptive p53 Gene Mutations in Squamous Cell Carcinoma of the Head and Neck. Clin. Cancer Res. 14: 366-369 [Abstract] [Full Text]  
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