QUANTITATIVE-ANALYSIS OF P53 PROTEIN IN NONSMALL CELL LUNG-CANCER ANDITS PROGNOSTIC VALUE

Accumulation of mutant p53 protein occurs frequently in human malignan cies, including 40-60% of non-small cell lung carcinomas. The implicat ions of such p53 over-expression, usually assessed by immunohistochemi cal techniques, for the prognosis of lung cancer patients remain undet ermined. In this study, we used a time-resolved immunofluorometric ass ay to measure p53 protein concentrations in extracts prepared from 86 primary non-small cell lung tumours and examined the associations betw een p53 protein levels (corrected for total protein) and other clinico -pathologic variables, including post-surgical disease-free and overal l survival, Contingency tables analysed by chi(2) tests revealed no si gnificant relationships between p53 status, defined by a median cut-of f point, and patient gender, age, disease stage, histologic grade and type, lymph node extension, smoking history and administration of adju vant chemotherapy or radiation, However, multivariate Cox proportional hazard regression analysis demonstrated a dose-response relationship between p53 concentration, expressed as a 4-level, quartile-divided va riable, and increased risk of relapse (p = 0.010) and death (p = 0.016 ). Patients whose tumours contained p53 concentrations exceeding the m edian value had over 3-fold higher risk of relapse (p = 0.002) and dea th (p = 0.007) than those whose tumours had lower p53 concentrations. We also provide evidence suggesting that the impact of p53 on survival is greater in patients with squamous cell carcinoma than in those wit h adenocarcinoma. Although the latter finding needs confirmation, our results suggest that application of an immunoassay of p53 protein on n on-small cell lung tumour extracts may identify patients at increased risk of unfavourable outcome, Int. J. Cancer (Pred. Oncol.) 79:494-501 , 1998. (C) 1998 Wiley-Liss, Inc.