Altered retinoblastoma and p53 protein status in non-small cell carcinoma of the lung: Potential synergistic effects on prognosis

Routinely processed pathological specimens from 119 patients with stage I and II adenocarcinomas or squamous cell carcinomas were examined by immunohistochemical analysis for altered retinoblastoma (RE) and/or p53 protein expression. Absent RE nuclear staining (RB^-) indicating loss of RE function occurred in 19 (16%) of the cases studied, whereas expression of a putative mutant p53 nuclear protein (p53⁺) was found in 54 (45%) of the tumors, The median survival was 39 versus 12 months for patients with RB⁺ and RB^- tumors, respectively (P = 0.05 by log rank analysis). Similarly, the median survival was 41 months for patients whose tumors had no expression of mutant p53 (p53^-) compared with 24 months for individuals with p53⁺ tumors (P = 0.01). These differences in survival, however, were not statistically significant by multivariate analysis. Nevertheless, individuals with RB^-/p53⁺ tumors had a significantly shorter median survival (12 months) than those with RB⁺/p53^- tumors (41 months), as determined by both log rank and multivariate analyses (P = 0.005 and 0.03, respectively). In addition, 66 large cell carcinomas from all stages were examined. again, a more significant difference in survival (48 versus g months) was found between patients with RB⁺/p53^- versus RB^-/p53⁺ tumors (P = 0.006). These results suggest that RE and p53 status might be used synergistically as prognostic factors in a subset of non-small cell lung carcinomas.