Endoglin (CD105) expression in angiogenesis of primary hepatocellular carcinomas: analysis using tissue microarrays and comparisons with CD34 and VEGF.
Few studies about angiogenesis in hepatocellular carcinoma (HCC) have been conducted and little is known about the significance of angiogenesis in HCC. In this study, the clinicopathological significance of tumor microvessel density (MVD) was assessed in 105 patients with HCC by immunohistochemical staining of CD105, CD34, and vascular endothelial growth factor (VEGF). Moreover, the use of the tissue microarray technique in evaluating angiogenesis of HCC was appraised. The MVD by CD105 immunostaining (MVD-CD105) was significantly lower in larger tumors (5 cm diameter as a cutoff point, p=0.001), more aggressive tumors, as indicated by venous infiltration (present vs absent, p=0.001), and tumors with advanced TNM stage (stage I & II vs stage III, p=0.011). A lower score of MVD by CD34 immunostaining (MVD-CD34) showed significant association only with venous invasion (p<0.001), whereas the MVD by CD105 immunostaining in tissue microarray (MVD-MA) was significantly lower only in larger sized tumors (p=0.043). Moreover, MVD-CD105 was positively associated with the expression intensity of VEGF (p=0.009), but not for MVD-CD34 (p=0.088). When median scores of MVD were used as cut-off points, the patients with higher score of MVD-CD105 had a significantly poorer prognosis in either disease-free or overall survival analysis (p=0.002 and p=0.009, respectively), whereas similar prognostic significance of MVD-CD34 was not observed in overall survival analysis (p=0.052) but was observed in disease-free survival analysis (p=0.022). No prognostic significance of MVD-MA was found in either disease-free or overall survival analysis (p=0.277 and p=0.712, respectively). These data demonstrate the superiority of CD105 over CD34 as a marker of angiogenesis in HCC and indicate that the tissue microarray technique is unsuitable for evaluating angiogenesis in HCC.
Yao
Yongzhong
Y
Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, 321 Zhongshan Road, 210008 Nanjing, P.R. China.
Pan
Yiming
Y
Chen
Jun
J
Sun
Xitai
X
Qiu
Yudong
Y
Ding
Yitao
Y
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002681:China; D000071063:Endoglin; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A