P53 PROTEIN ACCUMULATION IN LUNG CARCINOMAS OF PATIENTS EXPOSED TO ASBESTOS AND TOBACCO-SMOKE

Primary lung carcinomas often carry mutations in the p53 tumor suppres sor gene. Most of these mutations alter the conformation of the p53 pr otein into a more stable phenotype that makes it immunohistochemically detectable. Asbestos is a carcinogen that can cause deletions in chro mosomes and possibly also gene mutations. In this study we examined 70 primary lung carcinomas for p53 protein accumulation using a polyclon al antihuman p53 antibody, CM-1. Patients were interviewed about their occupational and smoking history and classified according to their an amnestical asbestos exposure. Presence of asbestos bodies (AB) was eva luated from histologic samples of peripheral nontumorous lung tissue u sing both 5-mu m-thick sections stained with Perls' iron and 30-mu m-t hick unstained sections. Abnormal accumulation of p53 protein was foun d in 36 tumors (51%), more often in patients exposed to asbestos than in patients without exposure (67% versus 40%, p = 0.027). Significant association was also noticed between the accumulation of p53 and the a sbestos content of lung tissue: 35% of the p53-positive patients had m ore than one AB/cm(2) compared with 14% of p53-negative cases (p = 0.0 46). Patients with strongly p53-positive tumors were heavier smokers(5 7.2 +/- 38.2 pack-years) than patients with p53-negative or lightly po sitive tumors (38.9 +/- 19.9 pack-years) (p = 0.017). Our findings ind icate that both asbestos exposure and heavy smoking can cause abnormal p53 protein accumulation suggestive of mutated p53.