Fhit expression in non-small cell lung cancer (NSCLC)
Background: The FHIT gene is commonly is affected by translocations and deletions. Although FHIT alterations at the DNA and RNA level are frequent in many types of tumors, the biological and clinical significance of these changes is not clear. In this study we aimed at correlating loss of the FHIT protein with a variety of genetic and clinical parameters in a well-characterized cohort of NSCLCs. Method: Paraffin sections of 94 non- small cell carcinomas were reacted with an anti-FHIT polyclonal antibody in a standard immunohistochemical reaction. Abnormal cases were characterized by complete loss of cytoplasmic staining. The staining results were then correlated with previously obtained data: LOH at 3p14, LOH at other loci, K-ras mutations, p53 abnormalities, staining patterns for RB and p16, and with a number of clinical parameters, including survival. Results: 52 of 94 tumors (55%) lacked cytoplasmic staining, with preserved reactivity in adjacent normal cells. Lack of staining correlated with LOH at 3p14, but not at other loci on 3p. It was significantly more common in squamous cell carcinomas compared to bronchiolo-alveolar and adenocarcinomas. Absent FHIT expression was inversely correlated with mutations in codon 12 of the K-ras gene. Lack of FHIT expression tended to correlate with the number of pack years smoked. There was however no statistically significant association with abnormal tumor suppressor gene expression, stage of disease or survival. Conclusion: Loss of FHIT expression was observed in over half of all NSCLCs, and was markedly more common in squamous cell carcinomas. Correlation with LOH at 3p14 provides additional evidence that the FHIT gene may be an important 3p14 deletional target in lung cancer. However, aberrant expression of this gene may not be of prognostic relevance.
Fong, KM; Geradts, J; Minna, JD; Zimmerman, RV
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