P53 IMMUNOSTAINING POSITIVITY IS ASSOCIATED WITH REDUCED SURVIVAL ANDIS IMPERFECTLY CORRELATED WITH GENE-MUTATIONS IN RESECTED NONSMALL CELL LUNG-CANCER - A PRELIMINARY-REPORT OF LCSG-871

We investigated the correlation of p53 abnormalities with survival in 85 patients with non-small cell lung cancer (NSCLC) who had undergone resection with curative intent as part of Lung Cancer Study Group (LCS G) 871. Our previous studies showed that only a subset of p53 mutation s in lung cancers result in overexpression. In addition, protein overe xpression has been described in the absence of mutation. Therefore, we determined both p53 protein overexpression (by immunostaining) and p5 3 and ras gene mutations (by single-strand conformation polymorphism a nd DNA sequencing) in this set of resected tumor specimens. Clinical f ollow-up data were available for 75 cases. Of the studied patients, 64 % showed p53 overexpression and 51% had mutant p53 sequences; however, the concordance rate was only 67%. There was a negative survival corr elation with positive p53 immunostaining (p=0.05), but not with the pr esence of gene mutations (p=0.62) in this group of patients. Overexpre ssion of p53 protein determined by immunostaining may contribute to ad verse outcome due to the ability of p53 to act as a dominant oncogene, or alternatively, overexpression may reflect ongoing DNA damage in th e tumor as a marker for a more aggressive behavior. When adjusted for stage, age, and gender by multivariate analysis, however, there was no independent impact of p53 overexpression on survival.