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 oncoproteins p53 and p185 was evaluated. These proteins have already been independently 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 sample of 102 NSCLC sufferers who underwent surgery for precocious disease during the period October 1991 to June 1994. The resected tumors were histologically classified and included 15 adenocarcinomas (37.5%), 1 large-cell carcinoma (2.5%), and 24 epidermoid (60%) carcinomas. The p53 concentration of tumor specimens was determined by luminescence immunoanalysis and was defined as positive if it was above the minimum value detectable by the method (0.01 ng/mg). The p185 protein was quantified by enzyme-linked immunoassay, and the 80th percentile of the frequency distribution was used as the reference cutoff value (348.8 U/mg). Survival and disease-free-survival (DFS) rates were estimated at 24 months after intervention. There were no significant differences in survival or DFS of patients with adenocarcinoma-type tumors for subjects with independent p185 values < 348.8 U/mg and those showing values ≥ 348.8 U/mg. Neither were there differences observed between patients with positive and negative p53 values. In patients with epidermoid-type tumors the cumulative survival was significantly higher in p53-negative than in p53-positive patients (p= 0.03) and was also higher in patients with p185 levels < 348.8 U/mg than in those with values ≥ 348.8 U/mg (p= 0.00001). These patients showed no significant differences with respect to recurrence rate. The possible synergistic behavior of p53 and p185 levels as a prognostic factor was evaluated 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 DFS between groups. Individual analysis of relative risks showed an increased risk of death and greater recurrence rate in patients with p185 levels ≥ 348.8 U/mg and a greater recurrence rate in patients with p53-positive values. Multivariate analysis established that the multiplicative, synergistic, prognostic effect of p53 and p185 was not significant. The existence of a significant, synergistic, prognostic effect of the p185 and p53 proteins in NSCLC could not be proven. However, a greater prognostic potential of the quantified overexpression of p185 with respect to that of p53 was established. An additive effect in the prognostic potential of both proteins was also observed (stratified analysis).