Role of expression of focal adhesion kinase in progression of hepatocellular carcinoma.
OBJECTIVE
Although hepatocellular carcinoma (HCC) is the most common cancer of the human liver, the mechanisms that regulate HCC development and progression remain unclear. The aim of this study was to investigate whether focal adhesion kinase (FAK) is involved in the progression of human HCC.


METHODS
Western blot analysis for FAK was performed on three HCC cell lines. We reviewed 64 consecutive patients who had undergone initial liver resection for HCC without preoperative treatment. Immunohistochemistry analysis for FAK was performed on paraffin-embedded tissues. FAK expression was confirmed by Western blot analysis in several clinical samples. We investigated the correlation between FAK expression and clinical outcome.


RESULTS
FAK proteins were detected in all HCC cell lines. Hepatocytes in the normal liver and chronic hepatitis with or without cirrhosis were negative for immunohistochemical staining for FAK expression. Cytoplasmic FAK expression was observed in 18 of 64 patients (28.1%), and this positive staining was correlated with gender (P < 0.05), a lower level of serum albumin (P < 0.05), and portal venous invasion (P < 0.01). Positive staining for FAK was associated with significantly poorer survival (P < 0.05). In multivariate analysis, FAK overexpression was an independent factor in determining the prognosis of patients.


CONCLUSIONS
These data suggest that FAK plays an important role in promoting tumor progression, especially vascular invasion, in HCC. FAK could play an important role in HCC progression and would be a novel target for HCC therapeutics as well as a prognostic marker.
Itoh
Shinji
S
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. itoshin@surg2.med.kyushu-u.ac.jp
Maeda
Takashi
T
Shimada
Mitsuo
M
Aishima
Shin-ichi
S
Shirabe
Ken
K
Tanaka
Shinji
S
Maehara
Yoshihiko
Y
D000368:Aged; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis*; D013997:Time Factors; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human