Use of possible synergistic expression of p53 and p185 as a prognostic tool for stage I non-small-cell lung cancer

The possible interaction between the quantified overexpression of the oncop roteins p53 and p185 was evaluated. These proteins have already been indepe ndently defined as prognostic factors in non-small-cell Lung cancer (NSCLC) , p53 and p185 levels were determined in stage I patients (n = 40) from a s ample of 102 NSCLC sufferers who underwent surgery for precocious disease d uring the period October 1991 to June 1994, The resected tumors were histol ogically classified and included 15 adenocarcinomas (37.5%), 1 large-cell c arcinoma (2.5%), and 24 epidermoid (60%) carcinomas. The p53 concentration of tumor specimens was determined by luminescence immunoanalysis and was de fined as positive if it was above the minimum value detectable by the metho d (0.01 ng/mg), The p185 protein was quantified by enzyme-linked immunoassa y, and the 80th percentile of the frequency distribution was used as the re ference cutoff value (348.8 U/mg). Survival and disease-free-survival (DFS) rates were estimated at 24 months after intervention. There were no signif icant differences in survival or DFS of patients with adenocarcinoma-type t umors fur subjects with independent p185 values < 348.8 U/mg and those show ing values greater than or equal to 348.8 U/mg, Neither were there differen ces observed between patients with positive and negative p53 values, In pat ients with epidermoid-type tumors the cumulative survival was significantly higher in p53-negative than in p53-positive patients (p = 0.03) and was al so higher in patients with p185 Levels < 348.8 U/mg than in those with valu es greater than or equal to 348.8 U/mg (p = 0.00001). These patients showed no significant differences with respect to recurrence rate. The possible s ynergistic behavior of p53 and p185 levels as a prognostic factor was evalu ated in patients with epidermoid-type tumors. p53-negative and p53-positive patients were grouped according to a p185 Level of less than or more than 348.8 U/mg. Significant differences were seen in both survival rates and DF S between groups. Individual analysis of relative risks showed an increased risk of death and greater recurrence rate in patients with p185 levels gre ater than or equal to 348.8 U/mg and a greater recurrence rate in patients with pS3-pnsitive values, Multivariate analysis established that the multip licative, synergistic, prognostic effect of p53 and p185 was not significan t. The existence of a significant, synergistic, prognostic effect of the p1 85 and p53 proteins in NSCLC could not be proven. However, a greater progno stic potential of the quantified overexpression of p185 with respect to tha t of p53 was established. An additive effect in the prognostic potential of both proteins was also observed (stratified analysis).