Expression of fragile histidine triad in primary hepatocellular carcinoma and its relation with cell proliferation and apoptosis.
OBJECTIVE
To evaluate the expression of fragile histidine triad (FHIT) gene protein, product of a candidate tumor suppressor, and to investigate the relationship between FHIT, cell apoptosis and proliferation, and pathological features of primary hepatocellular carcinoma (HCC).


METHODS
Forty-seven HCC and ten normal liver specimens were collected during surgical operation between 2001 and 2003. FHIT and proliferating cell nuclear antigen (PCNA) expression were detected by immunohistochemistry, and apoptotic level was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay on the tissue sections.


RESULTS
All normal liver tissues showed a strong expression of FHIT, whereas 28 of 47 (59.6%) carcinomas showed a significant loss or absence of FHIT expression (P = 0.001). The proportion of reduced FHIT expression in those carcinomas at stages III-IV (70.6%) and in those with extrahepatic metastasis (86.7%) showed an increasing trend compared with those at stages I-II (30.8%, P = 0.013) and those without metastasis (46.9%, P = 0.010) respectively. Apoptotic incidence in advanced TNM stage carcinoma and those with positive FHIT expression was higher than that in early stage carcinoma (P = 0.030) and in those with negative FHIT expression (P = 0.044) respectively. The proliferating potential of hepatocellular carcinoma was associated with FHIT expression (P = 0.016) and the aggressive feature (P = 0.019). Kaplan-Meier analysis demonstrated that the survival time of these 47 patients correlated with TNM stage, FHIT expression and metastasis.


CONCLUSIONS
There is marked loss or absence of FHIT expression, as well as abnormal apoptosis-proliferation balance in HCC. FHIT may play an important role in carcinogenesis and development of HCC.
Nan
Ke-Jun
KJ
Department of Oncology, First Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
Ruan
Zhi-Ping
ZP
Jing
Zhao
Z
Qin
Hai-Xia
HX
Wang
Hong-Yan
HY
Guo
Hui
H
Xu
Rui
R
D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D000328:Adult; D017209:Apoptosis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D002455:Cell Division / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D006639:Histidine / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000502:physiology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D012016:Reference Values; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D006639:Histidine; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase