Am. J. Respir. Crit. Care Med., Vol 150, No. 2, Aug 1994, 528-533.
p53 protein accumulation in lung carcinomas of patients exposed to asbestos and tobacco smoke
K Nuorva, R Makitaro, E Huhti, D Kamel, K Vahakangas, R Bloigu, Y Soini and P Paakko
Department of Pathology, University of Oulu, Finland.
Primary lung carcinomas often carry mutations in the p53 tumor suppressor
gene. Most of these mutations alter the conformation of the p53 protein
into a more stable phenotype that makes it immunohistochemically
detectable. Asbestos is a carcinogen that can cause deletions in
chromosomes and possibly also gene mutations. In this study we examined 70
primary lung carcinomas for p53 protein accumulation using a polyclonal
antihuman p53 antibody, CM-1. Patients were interviewed about their
occupational and smoking history and classified according to their
anamnestical asbestos exposure. Presence of asbestos bodies (AB) was
evaluated from histologic samples of peripheral nontumorous lung tissue
using both 5-microns-thick sections stained with Perls' iron and
30-microns-thick unstained sections. Abnormal accumulation of p53 protein
was found 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
asbestos content of lung tissue: 35% of the p53-positive patients had more
than one AB/cm2 compared with 14% of p53-negative cases (p = 0.046).
Patients with strongly p53-positive tumors were heavier smokers (57.2 +/-
38.2 pack- years) than patients with p53-negative or lightly positive
tumors (38.9 +/- 19.9 pack-years) (p = 0.017). Our findings indicate that
both asbestos exposure and heavy smoking can cause abnormal p53 protein
accumulation suggestive of mutated p53.
