AIM: 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. CONCLUSION: 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.
AIM: 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. CONCLUSION: 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.
Authors: Alba Rocco; Laslo Schandl; Jie Chen; Hongbing Wang; Zsolt Tulassay; Deirdre McNamara; Peter Malfertheiner; Matthias P A Ebert Journal: J Cancer Res Clin Oncol Date: 2003-03-04 Impact factor: 4.553
Authors: Francesco Trapasso; Agnieszka Krakowiak; Rossano Cesari; Jeffrey Arkles; Sai Yendamuri; Hideshi Ishii; Andrea Vecchione; Tamotsu Kuroki; Pawel Bieganowski; Helen C Pace; Kay Huebner; Carlo M Croce; Charles Brenner Journal: Proc Natl Acad Sci U S A Date: 2003-02-06 Impact factor: 11.205
Authors: S Takizawa; S Nakagawa; K Nakagawa; T Yasugi; T Fujii; K Kugu; T Yano; H Yoshikawa; Y Taketani Journal: Br J Cancer Date: 2003-04-22 Impact factor: 7.640
Authors: L D Barnes; P N Garrison; Z Siprashvili; A Guranowski; A K Robinson; S W Ingram; C M Croce; M Ohta; K Huebner Journal: Biochemistry Date: 1996-09-10 Impact factor: 3.162
Authors: H Andachi; K Yashima; M Koda; K Kawaguchi; A Kitamura; A Hosoda; Y Kishimoto; G Shiota; H Ito; M Makino; N Kaibara; H Kawasaki; Y Murawaki Journal: Br J Cancer Date: 2002-08-12 Impact factor: 7.640
Authors: Juliette Martin; Fabrice Magnino; Karin Schmidt; Anne-Christine Piguet; Ju-Seog Lee; David Semela; Marie V St-Pierre; Andrew Ziemiecki; Doris Cassio; Charles Brenner; Snorri S Thorgeirsson; Jean-François Dufour Journal: Gastroenterology Date: 2006-06 Impact factor: 22.682