EXPRESSION OF P53 ONCOPROTEIN IN NON-SMALL-CELL LUNG-CANCER - A FAVORABLE PROGNOSTIC FACTOR

Purpose: Mutation of the p53 gene is one of the most common genetic ab normalities found in lung cancer. The purpose of this study was to eva luate the prognostic value of p53 oncoprotein expression in patients w ith non-small-cell lung cancer (NSCLC). Patients and Methods: We studi ed 156 resected primary NSCLCs by the immunohistochemical staining tec hnique, 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 o f 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 car cinomas tended to express more p53 than adenocarcinomas. Since 50% pos itivity marked the most distinct change in overall survival duration ( P = .0008), we divided the cases into three groups, as follows: p53-ne gative (less than or equal to 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 r espective median survival durations of more than 65, 26, and 33 months (P = .002). The survival difference among the three groups was statis tically significant for non-squamous cell (P = .008), but not for squa mous cell (P = .17) carcinomas. Among lymph node-negative patients, th e 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 medi an survival durations for the low and negative groups were 21 and 18 m onths, respectively (P = .001). A Cox regression analysis with multipl e covariates showed that p53 positivity in more than 50% of tumor cell s was an independent prognostic factor for better outcome. Conclusion: These results suggest that high expression of p53 oncoprotein isa fav orable prognostic factor in a subset of patients with NSCLC. J Clin On col 13:1893-1903. (C) 1995 by American Society of Clinical Oncology.