Clinical significance of thrombospondin 1 expression in hepatocellular carcinoma.
OBJECTIVE
Thrombospondin 1 (THBS 1) is a matricellular protein capable of modulating angiogenesis. However, the actual role of THBS 1 in angiogenesis and tumor progression remains controversial. Hepatocellular carcinoma (HCC) is a hypervascular tumor characterized by neovascularization. The significance of THBS 1 in HCC remains unknown. In this study, the significance of THBS 1 in HCC was evaluated by correlating its expression with clinicopathological data. The possible role of THBS 1 in the angiogenesis of HCC was also studied by correlating its expression with vascular endothelial growth factor (VEGF) expression.


METHODS
Sixty HCC patients were recruited in this study. THBS 1 and VEGF protein expression in tumorous livers were localized by immunohistochemical staining and quantified by ELISA. THBS 1 mRNA was quantified by quantitative reverse transcription-PCR.


RESULTS
Immunohistochemical staining of THBS 1 was positive in HCC cells in 51.7% of patients and in stromal cells in 65% of patients. Tumor THBS 1 protein level was significantly correlated with its mRNA expression (P = 0.001) and was significantly correlated with tumor VEGF protein levels (P = 0.001). Its expression was significantly associated with the presence of venous invasion (P = 0.008) and advanced tumor stage (P = 0.049). High THBS 1 expression was also a prognostic marker of poor survival in HCC patients.


CONCLUSIONS
This study shows that high expression of THBS 1 is associated with tumor invasiveness and progression in HCC. THBS 1 appears to be a proangiogenic factor that stimulates angiogenesis in HCC in view of its positive correlation with VEGF expression.
Poon
Ronnie T
RT
Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong. poontp@hkucc.hku.hk
Chung
Ka Kit
KK
Cheung
Siu Tim
ST
Lau
Cecilia P
CP
Tong
See Wai
SW
Leung
Ka Ling
KL
Yu
Wan Ching
WC
Tuszynski
George P
GP
Fan
Sheung Tat
ST
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019700:Thrombospondin 1 / Q000096:biosynthesis*; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D012333:RNA, Messenger; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A