P53 GENE ABERRATIONS IN NON-SMALL-CELL LUNG CARCINOMAS FROM A SMOKINGPOPULATION

We examined 46 non-small-cell lung carcinomas (NSCLCs) for the presenc e of p53 mutations in exons 4-9, positive p53 immunostaining and loss of heterozygosity (LOH) in the TP53 locus. p53 mutations were detected in 13 tumour samples (28.3%), whereas overexpression of the p53 prote in was found in 30 of 45 (67%) samples. Allelic loss was found in 9 of 38 (23.6%) informative cases. The statistical analysis revealed no si gnificant correlation between p53 mutations and clinicopathological da ta, although mutations appear to occur more frequently in squamous cel l carcinomas (7 of 18) than in adenocarcinomas (2 of 15). All but thre e individuals in this study group smoked. In contrast to previous repo rts, we found a higher prevalence of GC-->AT transitions than of GC-TA transversions, as expected in a smoking population. A trend was found between p53-positive immunostaining and a history at heavy smoking (7 6-126 pack-years) and was inversely correlated with allelic deletion ( LOH) at the TP53 locus. Eight of the 12 NSCLCs containing p53 mutation s also had concomitant p53 overexpression, and it is of specific note that three of the four tumours containing p53 'mutations with no overe xpression of the p53 protein had either insertions or deletions in the p53 gene. No correlation was found between p53 mutations and fraction al allele loss or ras mutations. p53 mutations in this Merseyside popu lation in the UK do not appear to be as common as in other reports for NSCLC and exhibit predominance of GC-AT transitions preferentially at non-CpG sites, suggesting that other carcinogens in addition to those in tobacco smoke may be involved in NSCLC in the Merseyside area of t he UK.