Immunohistochemical detection of mutant p53 protein in small-cell lung cancer: relationship to treatment outcome.
We investigated the expression of mutant p53 proteins in small-cell lung cancer (SCLC) immunohistochemically, by identification of stabilized mutant p53 proteins with a much longer half-life than the wild-type protein. Of 103 tumor specimens obtained by transbronchial tumor biopsy for histologic diagnosis, 52 (50%) showed positive staining for p53 protein with a p53 monoclonal antibody, DO-1. Positive staining for p53 protein was not correlated with age, sex, performance status, lifetime cigarette consumption, serum concentration of neuron-specific enolase and extent of disease. Complete response rates in patients with a mutant p53 protein-positive tumor were significantly lower than those in p53-negative patients (25% versus 59%; P=0.0005, by chi-square test). Similarly, survival periods in patients with a mutant p53 protein-positive tumor were significantly shorter than those in mutant p53-protein-negative patients (10.8 months versus 20.6 months; P=0.0001, by generalized Wilcoxon test). Multivariate analysis using Cox's proportional hazards model revealed that the presence of mutant p53 protein is an independent factor associated with differences in overall survival (hazards ratio=2.72; 95% confidence interval, 1.71-4.34; P=0.0001). These observations suggest that the expression of mutant p53 proteins in SCLC may be an important factor predicting poor prognosis.
Gemba
K
K
Second Department of Internal Medicine, Okayama University Medical School, 2-5-1 Shikata-cho, 700-8558, Okayama, Japan.
Ueoka
H
H
Kiura
K
K
Tabata
M
M
Harada
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000378:metabolism; D016009:Chi-Square Distribution; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016159:Tumor Suppressor Protein p53