TP53 mutations and survival in squamous-cell carcinoma of the head and neck.
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.
Poeta
M Luana
ML
Johns Hopkins University, Baltimore, MD 21287, USA.
Manola
Judith
J
Goldwasser
Meredith A
MA
Forastiere
Arlene
A
Benoit
Nicole
N
Califano
Joseph A
JA
Ridge
John A
JA
Goodwin
Jarrard
J
Kenady
Daniel
D
Saunders
John
J
Westra
William
W
Sidransky
David
D
Koch
Wayne M
WM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53