Immunohistochemical detection of mutant
p53 protein in small-cell lung cancer: relationship to treatment
outcome.
Gemba K, Ueoka H, Kiura K,
Tabata M, Harada M
Second Department of Internal Medicine, Okayama
University Medical School, 2-5-1 Shikata-cho, 700-8558, Okayama,
Japan
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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.
