Endoglin (CD105) Expression in Angiogenesis of Primary Hepatocellular Carcinomas: Analysis using Tissue

Abstract. Few studies about angiogenesis in hepatocellular carcinoma (HCC) have been conducted and little is known about the signifi cance of angiogenesis in HCC. In this study, the clinicopathological signifi cance of tumor microvessel density (MVD) was assessed in 105 patients with HCC by immuno-histochemical 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. Th e MVD by CD105 immunostaining (MVD-CD105) was signifi cantly lower in larger tumors (5 cm diameter as a cutoff point, p = 0.001), more aggressive tumors, as indicated by venous infi ltration (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 signifi cant association only with venous invasion (p <0.001), whereas the MVD by CD105 immunostaining in tissue microarray (MVD-MA) was signifi cantly 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 signifi cantly poorer prognosis in either disease-free or overall survival analysis (p = 0.002 and p = 0.009, respectively), whereas similar prognostic signifi cance 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 signifi cance of MVD-MA was found in either disease-free or overall survival analysis (p = 0.277 and p = 0.712, respectively). Th ese 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