OVEREXPRESSION OF BCL-2 AND MUTATIONS IN P53 AND K-RAS IN RESECTED HUMAN NONSMALL CELL LUNG CANCERS

We investigated expression of Bcl-2, mutations in p53, and K-ras oncog ene in 51 resected human nonsmall cell lung cancers. The studies were designed to test for the possibility of cooperativity between these on cogenes and p53 in the pathogenesis of lung cancer. An inverse relatio nship was found between expression of Bcl-2 and mutant p53 by immunohi stochemistry (P < 0.01; Fisher exact test), suggesting that either Bcl -2 overexpression or mutations in p53 may fulfill a critical function in the pathogenesis of human non-small cell lung cancers. Tumors that harbored K-ras codon 12 mutations seldom had p53 mutations or overexpr essed Bcl-2. Statistical analysis of these data showed that mutations in p53 and K-ras or overexpression of Bcl-2 and mutations in K-ras occ urred at a frequency that could be explained only by chance [P > 0.1 i n each case (Fisher exact tests)]. This suggests that cooperativity be tween mutant K-ras and mutant p53 or mutant K-ras and overexpressed Bc l-2 is not a common mechanism in the pathogenesis of human non-small c ell lung cancers.