Loss of FHIT Expression in Non-Small Cell Lung Cancer: The Clinical Significance and Effects on Apoptosis and Cell Proliferation Cycle

Kim, Hak Ryul; Yang, Sei Hoon; Jeong, Eun Taik

Abstract

BACKGROUND: 3p deletion has been shown to be the most frequently occurring change in lung cancers, suggesting the presence of a tumor suppressor gene in this region. Recent attention has focused on a candidate 3p14.2 tumor suppressor gene, FHIT. Therefore, the association of the expression of FHIT, with apoptosis, cell proliferation cycle and the clinicopathological features, including survival, were investigated.
MATERIALS AND METHODS
83 patients with non-small cell lung cancer, who underwent curative operation, between Jan. 1996 and Aug. 2000, at the Wonkwang university hospital, were analyzed. The expression of the FHITwas identified by immunohistochemical staining, and rate of apoptosis and cell
RESULTS
43% (36/83) of patients exhibited no FHIT expression. The rates of FHIT loss were 52% (28/54), 22% (5/23), 50% (3/6); 30% (11/37), 48% (16/33), 69% (9/13); 54% (30/56) and 22% (6/27), in squamous cell cancers, adenocarcinomas, large cell cancers, TNM stages I, II and III, smokers and non-smokers, respectively. All the differences in FHIT loss rates, according to the histopathology, TNM stages and smoking habits, were statistically significant. The median survival time and 2-year survival rate of the FHIT(-) group were 24 months and 44%, and those of the FHIT(+) group were 25 months and 51% (p>0.05), respectively. The apoptotic rate of the FHIT(-) and FHIT(+) groups were 50.72 (+/- 13.93) and 59.38 (+/-14.33)%, respectively (p=0.01). The S- and G1-phase fractions of the FHIT(-) and FHIT(+) groups were 13.93 (+/-7.35) and 51.50(+/-23.15)% and 15.65(+/-6.59) and 54.16 (+/-20.25)%, respectively (p>0.05).
CONCLUSION
The loss of FHIT expression was increased to a greater extent with advancing TNM stage, smoking habits and squamous cell cancer compared to the adenocarcinomas. However, no survival differences were found according to the expression of FHIT. The apoptotic rate of the FHIT(+) group was greater than in the FHIT(-) group, but differences in the S- and G1-phase fractions, according to the expression of the FHIT, were not found.