Microvascular density of regenerative nodule to small hepatocellular carcinoma by automated analysis using CD105 and CD34 immunoexpression

Abstract

BackgroundAngiogenesis is a proliferative process resulting in the development of new blood vessels from existing endothelial cells and is considered crucial for tumor growth and metastasis. Tumor angiogenesis can be quantified by microvascular density (MVD), which is evaluated in highly vascularized tumor areas (hot spots) by immunohistochemical assays using CD34 and CD31 pan-endothelial antibodies. More recently, CD105 has been successfully used for some tumor types because it could discriminate neovascularization. The expression of CD34 and CD105 in hepatocellular carcinomas (HCC) and hepatic precancerous lesions has been reported—although the results for CD105 are controversial—but to the best our knowledge, CD105 has not been previously investigated in dysplastic nodules (DN). We investigated and compared MVD-CD34 and MVD-CD105 immunoexpression in tissues containing different stages of hepatocarcinogenesis, including DN.MethodsA total of 31 regenerative nodules (RN), 26 DN and 25 small HCC from explants were used for immunohistochemical tests with CD34 and CD105 antibodies. Antibody expression was quantified by computerized image analysis measurement of MVD, areas containing highly positive endothelial cells within the nodules.ResultsThe median MVD for CD34 was higher in HCC than in DN and RN (p < 0.01), and was higher in DN compared with RN (p = 0.033). In contrast, MVD with CD105 was higher in RN, and the difference was significant in RN and DN compared with HCC (p = 0.019 and p = 0.012, respectively). When MVD with CD34 and CD105 were compared within a single group, there was a significant predominance of CD105 in RN and DN (p < 0.01). In addition, MVD-C34 in HCC predominated compared with MVD-CD105, but the difference was not statistically significant (p = 0.128).ConclusionsThis study identified a close relationship between CD105 and liver cirrhosis, and that CD34 antibody is a good endothelial marker for hepatic carcinogenesis. There was no difference between the use of CD105 and CD34 antibodies in preneoplastic lesions.

Immunohistochemical angiogenic biomarkers in hepatocellular carcinoma and cirrhosis: correlation with pathological features

“…It is possible that the lack of association between MVD-CD105 expression and microvascular invasion in the present study resulted from the smaller average size of the advanced lesions that were examined (4.8 cm); in contrast to our current work, Ho et al compared tumors that were ≤5 cm in diameter with those >5 cm in diameter. Such findings in combination with our previous observations 29 suggest that MVD-CD105 expression decreases during carcinogenesis and tumor progression.…”

Hydroxysafflor yellow A inhibits angiogenesis of hepatocellular carcinoma via blocking ERK/MAPK and NF-κB signaling pathway in H22 tumor-bearing mice

“…CD105 is evaluated as the marker of neovascularization (Paschoal et al, 2014). VEGFA and bFGF are the important growth factors implicated in cancer angiogenesis and can also be used as tumor markers (Kammerer et al, 2013;Zetter, 1998).…”

Silencing of hypoxia inducible factor‐1α by RNA interference inhibits growth of SK‐NEP‐1 Wilms tumour cells in vitro, and suppresses tumourigenesis and angiogenesis in vivo

“…Here, we examined the microvascular density in the xenograft tumours by immunohistochemical staining for CD34, a typical marker of vascular endothelial cells. 11 As shown in Fig. 5a, the immune reactivity to CD34 was greatly reduced in the tumours with constitutive silencing of HIF-1a, implying compromised angiogenesis in the tumours with low HIF-1a expression.…”

“…Intra‐tumoural hypoxia stimulates angiogenesis. Here, we examined the microvascular density in the xenograft tumours by immunohistochemical staining for CD34, a typical marker of vascular endothelial cells . As shown in Fig.…”