Altered Fhit Expression and Its Relationship with p53 Overexpression in Non-small Cell Lung Cancers

Myong, Na Hye; Yoon, Seok Jun

Abstract

BACKGROUND: FHIT (Fragile histidine triad), the tumor suppressor gene at 3p14.2, encompasses the FRA3B fragile site and is a common target of deletions in primary human epithelial cancers, including those of the lung, head and neck, stomach, cervix, breast, and kidney. We investigated the association of Fhit expression with clinicopathologic features, including smoking history, and tried to correlate its altered expression with p53 overexpression in 45 non-small cell lung cancers.
METHODS
Immunohistochemical staining was performed on the paraffin sections, using primary anti-GST-Fhit and anti-human p53 antibodies. A four-tiered scoring system, incorporateing both intensity of staining and the percentage of cells stained was used. Composite scores < or = 3 were defined as a marked reduction or loss of Fhit or p53 protein expression.
RESULTS
Among the 45 tumors analyzed, 35 (77.8%) were markedly reduced or negative for Fhit protein expression. The reduced expression of Fhit protein was found to be significantly higher in smokers than in nonsmokers and also higher in squamous carcinoma compared with adenocarcinoma. Fhit and p53 alterations were found to be independent events, because there was no significant difference of Fhit-negativity between p53-positive and -negative groups.
CONCLUSION
These results indicate that the Fhit alteration preferentially occurs in smokers and in the squamous type of non-small cell lung carcinomas. In addition, the results support the notion that Fhit alterations play an important role in the pulmonary carcinogenesis.