Mutations of the p53 gene as a predictor of poor prognosis in patients with non-small-cell lung cancer.
BACKGROUND
Inactivation of the p53 tumor suppressor gene (also known as TP53) through a point mutation and/or loss of heterozygosity is one of the most common genetic changes found in various types of human tumors.


OBJECTIVE
Our purpose was to investigate the relationship between the presence of p53 gene mutations and survival of patients with non-small-cell lung cancer (NSCLC) of all stages who underwent surgery with preoperative curative intent as a routine therapeutic intervention. The prognostic significance of factors like sex, age, tumor histology, and the stage of the disease was also evaluated.


METHODS
We analyzed 120 tumor specimens from patients with histologically confirmed NSCLC for p53 mutations occurring in exons 5 through 8 by polymerase chain reaction-single-strand conformation polymorphism assay of genomic DNA. Univariate and multivariate analyses were performed to assess the association between p53 mutations and the survival of the NSCLC patients.


RESULTS
Fifty-one (43%) of 120 tumor specimens showed p53 mutations. Overall, the p53 mutations did not correlate with sex, age, or the clinical stage of the disease but showed frequent association with tumors of squamous cell histology. Univariate analysis revealed that the patients with p53 mutations survived for a significantly shorter period of time after surgery than those without the mutations (P = .0100, logrank test). The presence of p53 mutations was a significant prognostic factor in the patients with advanced disease (stages IIIA through IV) (P = .0091) but not in those with early disease (stages I and II) (P = .2837). Multivariate analysis using the Cox proportional hazards model found independent prognostic significance for p53 mutations (hazards ratio [HR] = 1.84; P = .018) and advanced disease stage (HR = 2.20; P = .003). The model also predicted the lower risk for female patients (HR = 0.51; P = .040).


CONCLUSIONS
The occurrence of p53 mutations in some NSCLC tumors may be independently associated with a shortened overall survival and may be of somewhat more prognostic significance in patients with advanced stage than in those with early stage of the disease.


CONCLUSIONS
Detection of p53 mutations may help in the selection of NSCLC patients suitable for appropriate investigational therapeutic strategies in view of improving their survival and quality of life.
Mitsudomi
T
T
Department of Surgery II, University of Occupational and Environmental Health, Kitakyushu, Japan.
Oyama
T
T
Kusano
T
T
Osaki
T
T
Nakanishi
R
R
Shirakusa
T
T
D000368:Aged; D000704:Analysis of Variance; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality; D005091:Exons / Q000235:genetics; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D009154:Mutation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis