Expression of p53 oncoprotein in non-small-cell lung cancer: a favorable prognostic factor.

Abstract

PURPOSE Mutation of the p53 gene is one of the most common genetic abnormalities found in lung cancer. The purpose of this study was to evaluate the prognostic value of p53 oncoprotein expression in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS We studied 156 resected primary NSCLCs by the immunohistochemical staining technique, using the p53 antibody DO7. There were 81 adenocarcinomas, 16 large-cell carcinomas, and 59 squamous cell carcinomas; stages were I in 67, II in 30, and III in 59 cases. For each tumor, the percentage of p53 positivity was calculated by scoring a minimum of 1,000 cells on an arbitrary intensity scale of 0 to 3+. RESULTS Overall, 103 (66%) tumors expressed p53 in more than 0.1% of cells, and squamous cell carcinomas tended to express more p53 than adenocarcinomas. Since 50% positivity marked the most distinct change in overall survival duration (P = .0008), we divided the cases into three groups, as follows: p53-negative (< or = 0.1%, n = 53), low p53 (0.1% to 50%, n = 54), and high p53 (> 50%, n = 49). Overall, patients in the high-p53 group survived longer than those in the low or negative groups, with respective median survival durations of more than 65, 26, and 33 months (P = .002). The survival difference among the three groups was statistically significant for non-squamous cell (P = .008), but not for squamous cell (P = .17) carcinomas. Among lymph node-negative patients, the survival difference between groups was not statistically significant. However, among lymph node-positive patients (n = 78), more than 65% of the high-p53 group survived for more than 70 months, while the median survival durations for the low and negative groups were 21 and 18 months, respectively (P = .001). A Cox regression analysis with multiple covariates showed that p53 positivity in more than 50% of tumor cells was an independent prognostic factor for better outcome. CONCLUSION These results suggest that high expression of the p53 oncoprotein is a favorable prognostic factor in a subset of patients with NSCLC.