Skip to main content

Advertisement

SpringerLink
Log in

Expression of endocan and vascular endothelial growth factor and their correlation with histopathological prognostic parameters in pheochromocytoma

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Objective

Endocan and vascular endothelial growth factor (VEGF) are markers expressed in various cancer types that are highly vascular, and they have prognostic significance for these cancers. In this study, we aimed to show the expression of endocan and VEGF in pheochromocytoma tumor tissues and to evaluate their correlations with histopathological parameters.

Material and methods

Thirty-eight patients who had been operated for pheochromocytoma were included in the study. As the control group, 28 subjects whose specimens contained normal adrenal medulla tissue were included. The formalin-fixed paraffin-embedded specimens of pheochromocytoma patients were evaluated for Pheochromocytoma of the Adrenal gland Scaled Score (PASS). Sections were then stained for immunohistochemical analysis. The degree of endocan and VEGF positivity was determined by the proportion of stained cells on a negative to strong scale.

Results

Endocan (p < 0.001) and VEGF (p = 0.004) expressions were found to be significantly higher in the pheochromocytoma group than in the control group. In the pheochromocytoma group, total PASS score (r = 0.714; p < 0.001) and most of the PASS score components were positively correlated with the level of endocan expression. Median Ki-67 index (p = 0.010), total PASS score (p < 0.001), tumor cell spindling (p = 0.048), and nuclear pleomorphism (p = 0.030) were higher in pheochromocytoma with VEGF expression than in those without.

Conclusion

If our findings are supported by studies with a larger sample size, we think that endocan has the potential to be used both as a tumor marker and in predicting malignancy potential in patients with pheochromocytoma, and that the detection of VEGF expression in these tumors is also associated with an increase in malignancy potential.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. L. Amar, J. Bertherat, E. Baudin et al. Genetic testing in pheochromocytoma or functional paraganglioma. J. Clin. Oncol. 23(34), 8812–8818 (2005)

    Article  CAS  PubMed  Google Scholar 

  2. J.W. Lenders, Q.Y. Duh, G. Eisenhofer et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 99(6), 1915–1942 (2014)

    Article  CAS  PubMed  Google Scholar 

  3. P.F. Plouin, P. Fitzgerald, T. Rich, et al. Metastatic pheochromocytoma and paraganglioma: focus on therapeutics. Horm. Metab. Res. 44(5), 390–399 (2012)

    Article  CAS  PubMed  Google Scholar 

  4. L.D. Thompson, Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases. Am. J. Surg. Pathol. 26(5), 551–566 (2002)

    Article  PubMed  Google Scholar 

  5. A. Kali, K.S. Shetty, Endocan: a novel circulating proteoglycan. Indian J. Pharmacol. 46(6), 579–583 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. M. Delehedde, L. Devenyns, C.A. Maurage, R.R. Vivès, Endocan in cancers: a lesson from a circulating dermatan sulfate proteoglycan. Int. J. Cell Biol. 2013, 705027 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  7. X. Huang, C. Chen, X. Wang et al. Prognostic value of endocan expression in cancers: evidence from meta-analysis. Onco Targets Ther. 9, 6297–6304 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  8. C.A. Maurage, E. Adam, J.F. Mineo et al. Endocan expression and localization in human glioblastomas. J. Neuropathol. Exp. Neurol. 68(6), 633–641 (2009)

    Article  CAS  PubMed  Google Scholar 

  9. H. Jiang, X.G. Fu, Y.T. Chen, Serum level of endothelial cell-specific molecule-1 and prognosis of colorectal cancer. Genet. Mol. Res. 14(2), 5519–5526 (2015)

    Article  CAS  PubMed  Google Scholar 

  10. J.H. Kim, M.Y. Park, C.N. Kim et al. Expression of endothelial cell-specific molecule-1 regulated by hypoxia inducible factor-1alpha in human colon carcinoma: impact of ESM-1 on prognosis and its correlation with clinicopathological features. Oncol. Rep. 28(5), 1701–1708 (2012)

    Article  CAS  PubMed  Google Scholar 

  11. K. Ozaki, N. Toshikuni, J. George et al. Serum endocan as a novel prognostic biomarker in patients with hepatocellular carcinoma. J. Cancer 5(3), 221–230 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  12. K. Hata, Y. Watanabe, H. Nakai, T. Hata, H. Hoshiai, Expression of the vascular endothelial growth factor (VEGF) gene in epithelial ovarian cancer: an approach to anti-VEGF therapy. Anticancer Res. 31(2), 731–737 (2011)

    CAS  PubMed  Google Scholar 

  13. M. Raica, L. Mogoantă, A.M. Cîmpean et al. Immunohistochemical expression of vascular endothelial growth factor (VEGF) in intestinal type gastric carcinoma. Rom. J. Morphol. Embryol. 49(1), 37–42 (2008)

    CAS  PubMed  Google Scholar 

  14. N. Srabovic, Z. Mujagic, J. Mujanovic-Mustedanagic et al. Vascular endothelial growth factor receptor-1 expression in breast cancer and its correlation to vascular endothelial growth factor a. Int. J. Breast Cancer 2013, 746749 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  15. J. Jacobsen, K. Grankvist, T. Rasmuson, A. Bergh, G. Landberg, B. Ljungberg, Expression of vascular endothelial growth factor protein in human renal cell carcinoma. BJU Int. 93(3), 297–302 (2004)

    Article  CAS  PubMed  Google Scholar 

  16. P. Carmeliet, R.K. Jain, Angiogenesis in cancer and other diseases. Nature 407(6801), 249–257 (2000)

    Article  CAS  PubMed  Google Scholar 

  17. J. Favier, P.F. Plouin, P. Corvol, J.M. Gasc, Angiogenesis and vascular architecture in pheochromocytomas: distinctive traits in malignant tumors. Am. J. Pathol. 161(4), 1235–1246 (2002)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. A.A. Ucuzian, A.A. Gassman, A.T. East, H.P. Greisler, Molecular mediators of angiogenesis. J. Burn Care Res. 31(1), 158–175 (2010)

    Article  PubMed  Google Scholar 

  19. J.C. Varghese, P.F. Hahn, N. Papanicolaou, W.W. Mayo-Smith, J.A. Gaa, M.J. Lee, MR differentiation of phaeochromocytoma from other adrenal lesions based on qualitative analysis of T2 relaxation times. Clin. Radiol. 52(8), 603–606 (1997)

    Article  CAS  PubMed  Google Scholar 

  20. P.P. Parikh, G.A. Rubio, J.C. Farra, J.I. Lew, Nationwide review of hormonally active adrenal tumors highlights high morbidity in pheochromocytoma. J. Surg. Res. 215, 204–210 (2017)

    Article  CAS  PubMed  Google Scholar 

  21. Q. Liu, G. Djuricin, E.D. Staren et al. Tumor angiogenesis in pheochromocytomas and paragangliomas. Surgery 120(6), 938–943 (1996)

    Article  CAS  PubMed  Google Scholar 

  22. H. Ohji, I. Sasagawa, O. Iciyanagi, Y. Suzuki, T. Nakada, Tumour angiogenesis and Ki-67 expression in phaeochromocytoma. BJU Int. 87(4), 381–385 (2001)

    Article  CAS  PubMed  Google Scholar 

  23. K. Salmenkivi, P. Heikkilä, J. Liu, C. Haglund, J. Arola, VEGF in 105 pheochromocytomas: enhanced expression correlates with malignant outcome. APMIS 111(4), 458–464 (2003)

    Article  PubMed  Google Scholar 

  24. A. Zielke, M. Middeke, S. Hoffmann et al. VEGF-mediated angiogenesis of human pheochromocytomas is associated to malignancy and inhibited by anti-VEGF antibodies in experimental tumors. Surgery 132(6), 1056–1063 (2002)

    Article  PubMed  Google Scholar 

  25. B.D. Grigoriu, F. Depontieu, A. Scherpereel et al. Endocan expression and relationship with survival in human non-small cell lung cancer. Clin. Cancer Res. 12(15), 4575–4582 (2006)

    Article  CAS  PubMed  Google Scholar 

  26. X. Leroy, S. Aubert, L. Zini et al. Vascular endocan (ESM-1) is markedly overexpressed in clear cell renal cell carcinoma. Histopathology 56(2), 180–187 (2010)

    Article  PubMed  Google Scholar 

  27. H. Jiang, X.G. Fu, Y.T. Chen, Serum level of endothelial cell-specific molecule-1 and prognosis of colorectal cancer. Genet. Mol. Res. 14(2), 5519–5526 (2015)

    Article  CAS  PubMed  Google Scholar 

  28. S. Moog, F. Castinetti, C. DoCao et al. Recurrence-free survival analysis in locally advanced pheochromocytoma: first appraisal. J. Clin. Endocrinol. Metab. 106(9), 2726–2737 (2021)

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported by the Scientific Research Fund of Necmettin Erbakan University.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Division of Endocrinology and Metabolism, Tokat State Hospital, Tokat, Turkey

    Muhammet Kocabaş

  2. Department of Internal Medicine, Division of Endocrinology and Metabolism, Muş State Hospital, Muş, Turkey

    Mustafa Can

  3. Department of Internal Medicine, Division of Endocrinology and Metabolism, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey

    Melia Karaköse, Mustafa Kulaksizoğlu & Feridun Karakurt

  4. Department of Pathology, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey

    Hacı Hasan Esen

Authors
  1. Muhammet Kocabaş
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mustafa Can
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Melia Karaköse
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hacı Hasan Esen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mustafa Kulaksizoğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Feridun Karakurt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mustafa Can.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethics approval

The Ethics Committee of the Necmettin Erbakan University (NEU) Meram Medical Faculty approved the study (decision no: 2020/2504 and date: 22.05.2020).

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kocabaş, M., Can, M., Karaköse, M. et al. Expression of endocan and vascular endothelial growth factor and their correlation with histopathological prognostic parameters in pheochromocytoma. Endocrine 82, 638–645 (2023). https://doi.org/10.1007/s12020-023-03489-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-023-03489-2

Keywords

Search

Navigation