High expression of CD34-positive sinusoidal endothelial cells is a risk factor for hepatocellular carcinoma in patients with HCV-associated chronic liver diseases.
CD34 has been widely used for the assessment of sinusoid-like neoangiogenesis in hepatocellular carcinoma (HCC). Recently, it was demonstrated that CD34-positive cells isolated from human peripheral blood differentiate into endothelial cells and contribute to neoangiogenesis in adults. We investigated the localization and the substantial role of CD34-positive endothelial cells in the liver with hepatitis C virus (HCV)--associated chronic liver diseases. Liver tissue sections obtained by biopsy from 56 patients with HCV-associated chronic liver diseases by were examined immunohistochemically using anti-CD34, anti-von Willebrand factor (vWF), and anti-vascular endothelial growth factor (VEGF) antibodies. CD34 was stained in the sinusoid, showing dotty, linear, semicircular, or circular patterns. However, sinusoidal expression of vWF was not substantially identified in the same specimens, indicating the existence of sinusoidal CD34-positive but vWF-negative endothelial cells. We classified these cells as CD34 LI and found that CD34 LI was correlated with the expression of VEGF. Among 34 patients with advanced-stage disease, the cumulative incidence of HCC was significantly higher in patients with CD34 LI >or= 12 (n = 16) than in those with CD34 LI < 12 (n = 18; P = .009). Moreover, among several clinicopathologic risk factors, CD34 LI could be recognized as an independently significant factor for development of HCC (relative risk, 7.36; P = .019). We conclude that CD34-positive endothelial cells are regulated by several factors, such as VEGF, and might play a substantial role in hepatocarcinogenesis. Furthermore, high expression of CD34-positive sinusoidal endothelial cells is a risk factor for HCC in patients with HCV-associated chronic liver diseases.
Ohmori
S
S
First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie, Japan.
Shiraki
K
K
Sugimoto
K
K
Sakai
T
T
Fujikawa
K
K
Wagayama
H
H
Takase
K
K
Nakano
T
T
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000096:biosynthesis*; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000032:analysis; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016174:Hepacivirus / Q000276:immunology / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000098:blood supply / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008222:Lymphokines / Q000032:analysis; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor / Q000032:analysis
D018952:Antigens, CD34; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor