TP53 mutations and survival in squamous-cell carcinoma of the head and neck
M Luana Poeta1, Judith Manola, Meredith A Goldwasser
1Johns Hopkins University, Baltimore, MD 21287, USA.
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.
Insights
Disruptive TP53 mutations in head and neck cancers significantly reduce patient survival. These specific tumor suppressor gene alterations indicate a poorer prognosis after surgical treatment.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- TP53 gene mutations are frequent in cancer, often abrogating tumor-suppressor function.
- Squamous-cell carcinoma of the head and neck (HNSCC) frequently harbors TP53 alterations.
- Understanding the impact of TP53 mutations on HNSCC patient outcomes is crucial for treatment stratification.
Purpose of the Study:
- To investigate the association between TP53 mutational status and survival in patients with HNSCC.
- To differentiate the prognostic impact of disruptive versus nondisruptive TP53 mutations.
Main Methods:
- Prospective study of 560 HNSCC patients undergoing curative surgery.
- TP53 mutations analyzed using Affymetrix p53 chip and Surveyor/DHPLC.
- Mutations classified as disruptive or nondisruptive based on predicted protein structure impact.
Main Results:
- TP53 mutations detected in 53.3% of HNSCC tumors.
- Any TP53 mutation correlated with decreased overall survival (HR 1.4, P=0.009).
- Disruptive TP53 mutations showed a stronger association with reduced survival (HR 1.7, P<0.001) compared to nondisruptive ones.
Conclusions:
- Disruptive TP53 mutations are an independent negative prognostic factor in HNSCC.
- These findings highlight the clinical relevance of TP53 mutation type in HNSCC patient outcomes.
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