p53 Mutation and Locoregional Treatment Failure in Head and Neck Squamous Cell Carcinoma

作者: W. M. Koch , J. A. Brennan , M. Zahurak , S. N. Goodman , W. H. Westra

DOI: 10.1093/JNCI/88.21.1580

关键词:

摘要: Background: The p53 gene (also known as TP53) may be the most common genetic target involved in malignant transformation of human cells. Direct sequence analysis has demonstrated that alteration this occurs approximately 45% head and neck squamous cell carcinomas. consequences mutations these cancers with respect to tumor behavior patient survival have not been rigorously determined. Purpose: We evaluated implications relation control locoregional disease overall following radiation therapy. Methods: Data from 110 consecutive patients invasive who were treated primary therapy (given curative intent) or adjuvant (following complete surgical extirpation gross disease) included analysis. A 1.8-kilobase fragment encompassing exons 5-9 was amplified DNA stored (frozen) specimens; cloned sequenced by use standard techniques. Overall disease-free after completion estimated Kaplan-Meier method; comparisons made logrank test proportional hazards regression models. Reported P values are two-sided. Results: Fortyeight (44%) tumors had cells bearing mutations. risk recurrence either significantly greater (i.e., time shorter) for whose contained mutant genes (univariate model hazard ratio [HR] mutation versus wild-type = 2.2; 95% confidence interval [CTJ 1.2-4.1; =.02). presence regional lymph node metastases (presence absence, HR 2.0; CI 1.0-42; .05) treatment type (primary surgery plus therapy, 23; 1.2-4J; .01) also associated risks failure. primary, opposed adjuvant, remained significant factors multivariate No relationship between status (mutant wild-type, 1.1; 0.6-2.1; .66); however, a shown stage (stages III IV [more advanced] stages I II [less advanced], 33; 1.010.8; .05). Mutation age, sex, stage, site, status, degree differentiation, method. Conclusions: is an increased failure carcinoma [J Natl Cancer last 1996;88:1580-6]

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