Skip to main content
Log in

Evaluation and comparison of microvessel density using the markers CD34 and CD105 in regenerative nodules, dysplastic nodules and hepatocellular carcinoma

  • Original Article
  • Published:
Hepatology International Aims and scope Submit manuscript

Abstract

Purpose

The progression of hepatocellular carcinoma (HCC) is multifactorial and angiogenesis plays a fundamental role, mainly because HCC is a highly vascularized tumor.

Methods

In this study, we determined microvessel density (MVD) using the immunohistochemical markers, CD34 and CD105 (Endoglin), in 44 hepatectomy specimens, encompassing 44 malignant nodules (HCC), 44 regenerative nodules (RN), and 15 dysplastic nodules (DN). The evaluation included the determination of MVD in all nodules. For statistical analysis, a descriptive analysis was carried out using measurements of position and dispersion for continuous variables; ANOVA was used to compare between groups, considering p < 0.05 as statistically significant.

Results

We observed a significant difference when comparing CD34 and CD105 immunoexpression in HCC, DN, and RN. CD105 was predominantly expressed in the peripheral regions in HCC, with mean MVD scores of 6.2 ± 4.1 and 10.7 ± 4.4 at the center and periphery of the nodules, respectively, with significant differences between groups (p < 0.0001). CD34 had higher mean MVD scores than CD105 in HCC, with a more uniform positivity pattern. CD105 immunoexpression in DN exhibited a pattern similar to HCC. However, in RN, CD105 exhibited a higher MVD score in the central portion of the nodules. CD105 was expressed in a subset of newly formed microvessels in HCC and demonstrated an elevated mean MVD in cirrhotic or regenerative nodules.

Conclusions

MVD determined by CD34 and CD105 expression may be used as an additional parameter to distinguish benign from malignant liver nodules.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Tsukuma H, Hiyama T, Tanaka S, Nakao M, Yabuuchi T, Kitamura, et al. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 1993;328(25):1797–1801

    Article  CAS  PubMed  Google Scholar 

  2. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132(7):2557–2576

    Article  CAS  PubMed  Google Scholar 

  3. Theise ND, Park YN, Curado MP, et al. Hepatocellular carcinoma. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO Classification of Tumours of the Digestive System. Lyon: IARC Press; 2010. 205–216

    Google Scholar 

  4. Theise ND, Park YN, Kogiro M. Dysplastic nodules and hepatocarcinogenesis. Clin Liver Dis 2002;6(2):497–512

    Article  PubMed  Google Scholar 

  5. Villanueva A, Newell P, Chiang DY, Friedman SL, Llovet JM. Genomics and signaling pathways in hepatocellular carcinoma. Semin Liver Dis 2007;27(1):55–76

    Article  CAS  PubMed  Google Scholar 

  6. Pang RW, Joh JW, Johnson PJ, Monden M, Pawlik TM, Poon RT. Biology of hepatocellular carcinoma. Ann Surg Oncol 2008;15(4):962–971

    Article  PubMed  Google Scholar 

  7. Hytiroglou P. Morphological changes of early human hepatocarcinogenesis. Semin Liver Dis 2004;24(1):65–75

    Article  PubMed  Google Scholar 

  8. Park YN, Yang CP, Fernandez GJ, Cubukcu O, Thung S, Theise ND. Neoangiogenesis and sinusoidal “capillarization” in dysplastic nodules of the liver. Am J Surg Pathol 1998;22(6):656–662

    Article  CAS  PubMed  Google Scholar 

  9. Semela D, Dufour JF. Angiogenesis and hepatocellular carcinoma. J Hepatol 2004;41:864–880

    Article  PubMed  Google Scholar 

  10. Deli G, Jin CH, Mu R, Yang S, Liang Y, Chen D, et al. Immunohistochemical assessment of angiogenesis in hepatocellular carcinoma and surrounding cirrhotic liver tissues. World J Gastroenterol 2005;11:960–963

    PubMed  Google Scholar 

  11. International Working Party. Terminology of nodular hepatocellular lesions. Hepatology 1995;22(3):983–993

    Article  Google Scholar 

  12. Hytiroglou P, Park YN, Krinsky G, Theise ND. Hepatic precancerous lesions and small hepatocellular carcinoma. Gastroenterol Clin N Am 2007;36:867–887

    Article  Google Scholar 

  13. International Consensus Group for Hepatocellular Neoplasia. Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. Hepatology 2009;49(2):658–664

    Article  Google Scholar 

  14. Roncalli M, Borzio M, Di Tommaso L. Hepatocellular dysplastic nodules. Ann Ital Chir 2008;79(2):81–89

    PubMed  Google Scholar 

  15. Sakamoto M, Effendi K, Masugi Y. Molecular diagnosis of multistage hepatocarcinogenesis. Jpn J Clin Oncol 2010;40(9):891–896

    Article  PubMed  Google Scholar 

  16. Shiraha H, Yamamoto K, Namba M. Human hepatocyte carcinogenesis (review). Int J Oncol 2013;42(4):1133–1138

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285(21):1182–1186

    Article  CAS  PubMed  Google Scholar 

  18. Folkman J. Tumor angiogenesis. Adv Cancer Res 1985;43:175–203

    Article  CAS  PubMed  Google Scholar 

  19. Folkman J, Shing Y. Angiogenesis. J Biol Chem 1992;267(16):10931–10934

    CAS  PubMed  Google Scholar 

  20. Frachon S, Gouysse G, Dumortier J, Couvelard A, Nejjari M, Mion F, et al. Endothelial cell marker expression in dysplastic lesions of the liver: an immunohistochemical study. J Hepatol 2001;34(6):850–857

    Article  CAS  PubMed  Google Scholar 

  21. Di Carlo I, Fraggetta F, Lombardo R, Azzarello G, Vasquez E, Puleo S. CD34 expression in chronic and neoplastic liver diseases. Panminerva Med 2002;44(4):365–367

    PubMed  Google Scholar 

  22. Yang L, Lu W, Huang G, Wang W. Correlation between CD105 expression and postoperative recurrence and metastasis of hepatocellular carcinoma. BMC Cancer 2006;6:110

    Article  PubMed Central  PubMed  Google Scholar 

  23. Nakamura T. Changes in expression of bile canalicular CD10 and sinusoidal CD105 (endoglina) in peri-tumoral hepatic tissue. Tumori 2009;95(4):495–500

    CAS  PubMed  Google Scholar 

  24. Wang Y, Zhang XH, Guo P, Yan LN, He D. Tumor microvascular density detected by anti-CD105 and anti-CD34 in hepatocellular carcinoma patients and its predictive value of tumor recurrence after liver transplantation. Sichuan Da Xue Xue Bao Yi Xue Ban 2010;41(5):818–882

    Google Scholar 

  25. Ho JW, Poon RT, Sun CK, Xue WC, Fan ST. Clinicopathological and prognostic implications of endoglin (CD105) expression in hepatocellular carcinoma and its adjacent non-tumorous liver. World J Gastroenterol 2005;11(2):176–181

    CAS  PubMed  Google Scholar 

  26. Yu D, Zhuang L, Sun X, Chen J, Yao Y, Meng K, et al. Particular distribution and expression pattern of endoglin (CD105) in the liver of patients with hepatocellular carcinoma. BMC Cancer 2007;7:122

    Article  PubMed Central  PubMed  Google Scholar 

  27. Wang ZS, Wu LQ, Yi X, Geng C, Li YJ, Yao RY. Connexin-43 can delay early recurrence and metastasis in patients with hepatitis B-related hepatocellular carcinoma and low serum alpha-fetoprotein after radical hepatectomy. BMC Cancer 2013;13(1):306

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Compliance with ethical requirements and Conflict of interest

This study entitled was approved by the Ethics and Research Committee at the institution where it was held (Faculty of Medical Sciences, State University of Campinas, Sao Paulo) with registration number 638/2006. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Vanderlei Segatelli, Ebe Christie de Oliveira, Elaine Cristina de Ataide, Ilka de Fatima Santana Ferreira Boin and Cecilia Amelia Fazzio Escanhoela declare that they have no conflict of interest

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vanderlei Segatelli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Segatelli, V., de Oliveira, E.C., Boin, I.F.S.F. et al. Evaluation and comparison of microvessel density using the markers CD34 and CD105 in regenerative nodules, dysplastic nodules and hepatocellular carcinoma. Hepatol Int 8, 260–265 (2014). https://doi.org/10.1007/s12072-014-9525-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12072-014-9525-9

Keywords

Navigation