Loss of Fhit expression in non-small-cell lung cancer: correlation with molecular genetic abnormalities and clinicopathological features

The FHIT gene is located at a chromosomal site (3p14.2) which is commonly a ffected by translocations and deletions in human neoplasia. Although FHIT a lterations at the DNA and RNA level are frequent in many types of tumours, the biological and clinical significance of these changes is not clear. In this study we aimed at correlating loss of Fhit protein expression with a l arge number of molecular genetic and clinical parameters in a well-characte rized cohort of non-small-cell lung cancers (NSCLCs), Paraffin sections of 99 non-small-cell carcinomas were reacted with an anti-Fhit polyclonal anti body in a standard immunohistochemical reaction. Abnormal cases were charac terized by complete loss of cytoplasmic Fhit staining. The Fhit staining re sults were then correlated with previously obtained clinical and molecular data. Fifty-two of 99 tumours lacked cytoplasmic Fhit staining, with preser ved reactivity in adjacent normal cells. Lack of Fhit staining correlated w ith: loss of heterozygosity (LOH) at the FHIT 3p14.2 locus, but not at othe r loci on 3p; squamous histology; LOH at 17p13 and 5q but not with LOH at m ultiple other suspected tumour suppressor gene loci; and was inversely corr elated with codon 12 mutations in K-ras. Fhit expression was not correlated overall with a variety of clinical parameters including survival and was n ot associated with abnormalities of immunohistochemical expression of p53, RE, and p16. All of these findings are consistent with loss of Fhit protein expression being as frequent an abnormality in lung cancer pathogenesis as are p53 and p16 protein abnormalities and that such loss occurs independen tly of the commitment to the metastatic state and of most other molecular a bnormalities. (C) 2000 Cancer Research Campaign.