FHIT AND P53 GENE ABNORMALITIES IN BRONCHIOLOALVEOLAR CARCINOMAS - CORRELATIONS WITH CLINICOPATHOLOGICAL DATA AND K-RAS MUTATIONS

Bronchioloalveolar carcinoma (BAG) is a particular type of adenocarcin oma of the lung which accounts for up to 9 per cent of pulmonary malig nancies. The aetiology and pathogenesis of this unique neoplastic dise ase are still unclear. Three histological subtypes of BAC have been re cognized: mucinous, non-mucinous, and sclerosing. Of these, mucinous a nd sclerosing BAC have a worse prognosis than non-mucinous tumours. Th e different morphological patterns and clinical outcomes of the subtyp es of BAC suggest differences in their biological behaviour. Previous reports have shown in that the mucinous form of BAC is characterized b y constant mutations at codon 12 of the K-ras gene, whereas the other two histotypes show a frequency of K-ras mutations which is not differ ent from that observed in conventional lung adenocarcinomas. The prese nt study of a series of 51 BACs, previously investigated for K-ras gen e mutations, has evaluated the status of two other genes, p53 and FHIT , known to be frequently altered in non-small cell lung cancer. Loss o f heterozygosity at microsatellite-containing loci located within the FHIT gene was observed in 22 (43 per cent) BACs. The distribution of F HIT gene abnormalities was not statistically different in the three hi stological subtypes, p53 mutations were present in 13 (32 per cent) no n-mucinous/sclerosing BACs, while no mutations mere seen in mucinous t umours (P=0.039). Correlations with clinicopathological parameters sho wed that p53 mutations in BACs are associated with more aggressive tum ours. No correlations mere observed between FHIT or K-ras gene abnorma lities and clinicopathological data. In conclusion, these results indi cate that FHIT alterations are frequently involved in BAC tumourigenes is and that genetic changes in the p53 and K-ras genes can distinguish between different histotypes of BAG. (C) 1998 John Wiley & Sons, Ltd.