ALTERED RETINOBLASTOMA PROTEIN EXPRESSION AND PROGNOSIS IN EARLY-STAGE NON-SMALL-CELL LUNG-CARCINOMA

Background: Altered retinoblastoma (RB also known as RB1) gene expre ssion was initially found in a small cohort study to occur in five (22 %) of 23 patients with primary stage I and II non-small-cell lung carc inomas (NSCLCs). Putative mutation of the p53 gene (also known as TP53 ) has also been found to occur frequently in stage I and II NSCLCs and to be associated with more aggressive disease and a poorer prognosis. Purpose: Our purpose was to determine the Rb protein status in the sa me cohort that had been previously studied for their p53 protein statu s and to document whether loss of Rb protein expression was also an im portant factor in overall survival. Methods: One hundred one stage I o r II NSCLC specimens were analyzed by immunohistochemical staining. Th ese paraffin-embedded tumor sections were obtained from individual par affin blocks prepared for each patient in the previous study. Patient survival status was obtained from hospital and tumor registry records. Results: Altered Rb protein expression was found in 24 of 101 stage I and II NSCLCs. The median survival was 32 months for patients with Rb -positive (Rb+) tumors and 18 months for individuals in whom expressio n of Rb protein was absent or altered (Rb-) in tumor cells. Logrank an alysis of the differences in overall survival was statistically signif icant (P = .007). When these results were combined with the p53 status in the same tumor, the median survival was 12 months for those indivi duals who had theoretically the worst pattern (Rb-/p53(+)) and 46 mont hs for those patients with theoretically the best pattern (Rb+/p53(-)) (P < .001). The Rb+ and Rb- groups in this cohort were well balanced with respect to the distribution of age, disease stage, histologic typ es, p53 status, and sex. Using a multivariate proportional hazards reg ression model, both altered Rb and p53 status were found to be signifi cantly associated with poor prognosis (P = .005 and .012, respectively ) in the overall cohort. Conclusion: Altered Rb protein expression is an independent prognostic marker for overall decreased survival in ear ly-stage NSCLC as detected by absence of nuclear Rb protein staining. There appears to be a poorer prognosis when loss of Rb protein functio n and mutated p53 protein occur in the same tumor. Implications: If th ese findings can be confirmed in larger prospective studies, the resul ts would suggest that both the Rb and p53 status should be utilized as independent prognostic factors in early-stage NSCLC.