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 ca ncer (SCLC) immunohistochemically, by identification of stabilized mutant p 53 proteins with a much longer half-life than the wild-type protein. Of 103 tumor specimens obtained by transbronchial tumor biopsy for histologic dia gnosis, 52 (50%) showed positive staining for p53 protein with a p53 monocl onal antibody, DO-1. Positive staining for p53 protein was not correlated w ith age, sex, performance status, lifetime cigarette consumption, serum con centration of neuron-specific enolase and extent of disease. Complete respo nse rates in patients with a mutant p53 protein-positive tumor were signifi cantly lower than those in p53-negative patients (25% versus 59%; P = 0.000 5. by chi-square rest). Similarly. survival periods in patients with a muta nt p53 protein-positive turner were significantly shorter than those in mut ant p53-protein-negative patients (10.8 months versus 20.6 months: P = 0.00 01, by generalized Wilcoxon test). Multivariate analysis using Cox's propor tional hazards model revealed that the presence of mutant p53 protein is an independent factor associated with differences in overall survival (hazard s ratio = 2.72. 95% confidence interval, 1.71-4.34; P = 0.0001). These obse rvations suggest that the expression of mutant p53 proteins in SCLC may be an important factor predicting pool prognosis. (C) 2000 Elsevier Science Ir eland Ltd. All rights reserved.