PROGNOSTIC VALUE OF THE EXPRESSION OF P53, BCL-2, AND BAX ONCOPROTEINS, AND NEOVASCULARIZATION IN PATIENTS WITH RADICALLY RESECTED NON-SMALL-CELL LUNG-CANCER

Purpose: To assess the prognostic value of p53, bcl-2, bax, and neovas cularization in radically resected non-small-cell lung cancer (NSCLC) patients, Patients and Methods: Turners from 116 patients were assesse d by immunohistochemistry for expression of p53 (DO7 and PAb1081), bcl -2, and the quantification of microvessel density (CD-31). In addition , the expression of bar was assessed in 61 stage I tumors, The median levels of expression of each marker were used as cutoff points, Result s: p53 was not correlated to any patient or tumor characteristic, wher eas bcl-2 showed higher expression in squamous cell carcinomas (P < .0 01), bar expression was significantly related with male sex (P = .006) and adenocarcinoma type (P = .0013), p53 status, assessed with one mo noclonal antibody (MoAb), was not predictive for survival; however, th e combination of staining results obtained with two MoAbs identified t he DO7(-)/PAb 1801(+) tumors as chose with the worst prognosis, bcl-2 expression was associated with longer survival in stage I patients (P = .0169), The combined group expressing p53(+)(PAb1801)/bcl-2(-) had t he worst survival in stage I patients (P = .034) and in the whole seri es in comparison with the other combinations of the two oncoproteins. bax expression alone had no influence on survival of stage I patients, but patients with bax(+)/bcl-2(-) tumors had the worst prognosis (P = .02 in comparison with bax(+)/bcl-2(+)). Tumor neovascularization was not related with other factors, and patients with CD-31(+) tumors had a shorter survival duration than these with CD-31(-) tumors only in s tage II (P = .0283), By multivariate analysis including all patients, the presence of p53(+)/ bcl-2(-) tumor expression and large tumor diam eter (greater than or equal to 4cm) were independent prognostic factor s for shorter survival duration, For stage I, only the presence of bax (+)/ bcl-2(-) tumor expression had a significant negative influence on survival, Conclusion: The interaction and the regulation of new biolo gic markers, such as those involved in the apoptotic pathway, are comp lex, Combinations of the expression of several of them may give more v aluable information than the study of just one. Prognostic influence o f p53 staining varied depending on the choice of antibody and the comb ination of bcl-2(-) together with p53(+) (PAb1801) or with bax(+) had the worst influence on survival for patients with stage I NSCLC, (C) 1 997 by American Society of Clinical Oncology.