Correlation between CD105 expression and postoperative recurrence and metastasis of hepatocellular carcinoma

Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, PR China.
BMC Cancer (Impact Factor: 3.36). 02/2006; 6(1):110. DOI: 10.1186/1471-2407-6-110
Source: PubMed


Angiogenesis is one of the mechanisms most critical to the postoperative recurrence and metastasis of hepatocellular carcinoma (HCC). Thus, finding the molecular markers associated with angiogenesis may help identify patients at increased risk for recurrence and metastasis of HCC. This study was designed to investigate whether CD105 or CD34 could serve as a valid prognostic marker in patients with HCC by determining if there is a correlation between CD105 or CD34 expression and postoperative recurrence or metastasis.
Immunohistochemical staining for the CD105, CD34 and vascular endothelial growth factor (VEGF) antibodies was performed in 113 HCC tissue specimens containing paracarcinomatous tissue and in 14 normal liver tissue specimens. The quantitation of microvessels identified by anti-CD105 and anti-CD34 monoclonal antibodies and the semiquantitation of VEGF expression identified by anti-VEGF monoclonal antibody were analyzed in conjunction with the clinicopathological characteristics of the HCC and any available follow-up information about the patients from whom the specimens were obtained.
CD105 was not expressed in the vascular endothelial cells of any normal liver tissue or paracarcinomatous liver tissue but was expressed in the vascular endothelial cells of all HCC tissue. In contrast, CD34 was expressed in the vascular endothelial cells of normal liver tissue, paracarcinomatous tissue, and HCC tissue in the following proportions of specimens: 86.7%, 93.8%, and 100%, respectively. The microvascular densities (MVDs) of HCC determined by using an anti-CD105 mAb (CD105-MVD) and an anti-CD34 mAb (CD34-MVD), were 71.7 +/- 8.3 (SD) and 106.3 +/- 10.4 (SD), respectively. There was a significant correlation between CD105-MVD and CD34-MVD (r = 0.248, P = 0.021). Although CD34-MVD was significantly correlated with VEGF expression (r = 0.243, P = 0.024), CD105-MVD was more closely correlated (r = 0.300, P= 0.005). The correlation between microscopic venous invasion and CD105-MVD, but not CD34-MVD, was also statistically significant (r = 0.254, P = 0.018). Univariate analysis showed that CD105-MVD was significantly correlated with the 2-year overall survival rate (P = 0.014); CD34-MVD was not (P = 0.601). Multivariate analysis confirmed that CD105-MVD was an independent prognostic factor and that CD34-MVD was not.
The anti-CD105 mAb is an ideal instrument to quantify new microvessels in HCC as compared with anti-CD34 mAb. CD105-MVD as compared with CD34-MVD is relevant a significant and independent prognostic indicator for recurrence and metastasis in HCC patients.

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    • "The expression of CD105 and CD34 increased significantly with enhanced VEGF expression [23]. Expression of markers CD9, CD29, CD44, CD49d, and CD106 interfere with the proliferation and differentiation of hematopoietic stem cells. "
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    ABSTRACT: Background Stem cells constitute a group of great capacity for self-renewal, long-term viability, and multi-lineage potential. Several studies have provided evidence that adipose tissue represents an alternative source of stem cells, with the main benefit of adipose-derived stem cells being that they can be easily harvested from patients by a simple minimally invasive method and can be easily cultured. The aim of this study was to establish a culture protocol for obtaining and characterizing adipose-derived stem cells (ADSCs) from C57BL/6 J mice. Results The results showed that the yield, viability, and cell morphology obtained differ according to the age of isolated anatomic regions of the adipose tissue from ovarian and epididymis. The results of determination of cyclin D1 showed uniformity in the expression between different populations of ADSCs. A significant increase in the expression of caspase-3 active, was also observed in large cell populations from mice after 120 days. ADSCs were positive for mesenchymal markers CD90 and CD105, Nanog, SSEA-1, CD106, and VEGFR-1, and negative for hematopoietic markers CD34 and CD45. A large number of cells in S + G2/M phases was also observed for both sexes, demonstrating high proliferative capacity of ADSCs. Conclusions We observed that the adipose tissue of C57BL/6 J mice, isolated from the studied anatomic regions, is a promising source for obtaining pluripotent mesenchymal stem cells with high viability and proliferative response.
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    • "The significant elevation of CD105 expression was also observed in the serum of patients with cirrhosis compared to healthy subjects [31]. In contrast, Yang et al. did not observe CD105 immunoexpression in non-neoplastic cells around tumors [32], although we speculate that the peritumoral tissue analyzed was not cirrhotic. "
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    ABSTRACT: Angiogenesis 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. A 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. The 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). This 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.
    Full-text · Article · Feb 2014 · BMC Cancer
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    • "CD105-MVD reflects new vessel growth in HCC tissue and is an independent predictor of recurrence, metastasis, and vessel invasion in postoperative patients with HCC [25]. VEGF can substantially accelerate division and growth of vascular endothelial cells and angiogenesis. "
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    ABSTRACT: We studied the relationships among Cx43, CD105, and VEGF in specimens of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different serum AFP levels with respect to recurrence and metastasis. Expressions of Cx43, CD105, and VEGF in 234 HCC tissue specimens were examined using tissue microarray and immunohistochemistry. Cx43 mRNA expression was examined in 38 frozen HCC specimens using RT-PCR. Correlations between these expressions and tumor recurrence, metastasis, and prognosis were analyzed using Kaplan--Meier and Cox regression analyses. Cx43 expression correlated with early tumor recurrence (P = 0.001), disease-free survival (P = 0.026), and overall survival (P = 0.000) in patients with serum AFP < 400 ng/ml, but not in those with serum AFP >= 400 mug/L. Cx43 expression is an independent predictor of later recurrence and longer overall survival and is inversely correlated with expression of CD105 and VEGF (P = 0.018 and 0.023, respectively), histological differentiation (P = 0.002), vessel tumor embolism (P = 0.029), and focal number (P = 0.017). Immunohistochemistry showed that Cx43 expression in patients with low AFP was lower in patients with distant metastases than in those with no metastasis or those with liver metastasis. Patients with early recurrence expressed less Cx43 mRNA than did those with no recurrence (chi2 = 9.827, P = 0.002). Cx43 expression can delay early HCC recurrence, metastasis, and poor prognosis after radical hepatectomy in patients with HBV-related HCC and low AFP.
    Full-text · Article · Jun 2013 · BMC Cancer
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