Can metastasis and recurrence be detected with Endocan and Vascular Endothelial Growth Factor in thyroid papillary cancer?




thyroid papillary cancer, endocan, vascular endothelial growth factor, recurrence, metastasis


Background. Endocan is known to be associated with different type of malignancies and vascular endothelial growth factor (VEGF) has been shown to upregulate endocan expression. We purposed to determine whether the presence of disease recurrence and/or metastasis can be detected with pathological evaluation of endocan and VEGF in patients with thyroid papillary cancer. Materials and methods. This study was performed retrospectively between January 2005 and December 2015. Patients’ gender, age, also age at diagnosis, and duration of follow-up were recorded. The study group was divided into two groups comprised of patients with and without postoperative recurrence and/or metastasis. Pathological samples were treated with Anti-ESM-1 and Anti-VEGFA, staining percentage and density were evaluated. Results. A total of 59 patients (43 female and 16 male) were included. The mean age was 52.39 ± 13.75 years. Mean longest tumor diameter was found to be 21.31 ± 20.20 mm, and follow-up duration was 37.24 ± 32.68 months. Among the patients, 54.2 % had recurrence and/or metastasis, while 45.8 % did not have either. The percentage of endocan staining and density was 84.26 ± 20.32 and 2.56 ± 0.75 in the recurrence and/or metastases group, 75.56 ± 24.06 and 2.11 ± 1.02, respectively in the group without. Endocan staining and density was higher in the patients with recurrence and/or metastasis but not statistically significant (p = 0.077, p = 0.136, respectively). No significant difference was found between two groups in terms of VEGF staining and density. Conclusions. These markers might be further evaluated for determination their role in recurrence and/or metastasis of thyroid papillary carcinoma.


Download data is not yet available.


Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg. 2014 Apr;140(4):317-22. doi:10.1001/jamaoto.2014.1.

Eustatia-Rutten CF, Corssmit EP, Biermasz NR, Pereira AM, Romijn JA, Smit JW. Survival and death causes in differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2006 Jan;91(1):313-9. doi:10.1210/jc.2005-1322.

Kali A, Shetty KS. Endocan: a novel circulating proteoglycan. Indian J Pharmacol. 2014 Nov-Dec;46(6):579-83. doi:10.4103/0253-7613.144891.

Balta S, Mikhailidis DP, Demirkol S, Ozturk C, Celik T, Iyisoy A. Endocan: A novel inflammatory indicator in cardiovascular disease? Atherosclerosis. 2015 Nov;243(1):339-43. doi:10.1016/j.atherosclerosis.2015.09.030.

Sarrazin S, Adam E, Lyon M, et al. Endocan or endothelial cell specific molecule-1 (ESM-1): a potential novel endothelial cell marker and a new target for cancer therapy. Biochim Biophys Acta. 2006 Jan;1765(1):25-37. doi:10.1016/j.bbcan.2005.08.004.

Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004 Aug;25(4):581-611. doi:10.1210/er.2003-0027.

Soh EY, Duh QY, Sobhi SA, et al. Vascular endothelial growth factor expression is higher in differentiated thyroid cancer than in normal or benign thyroid. J Clin Endocrinol Metab. 1997 Nov;82(11):3741-7. doi:10.1210/jcem.82.11.4340.

Rennel E, Mellberg S, Dimberg A, et al. Endocan is a VEGF-A and PI3K regulated gene with increased expression in human renal cancer. Exp Cell Res. 2007 Apr 15;313(7):1285-94. doi:10.1016/j.yexcr.2007.01.021.

Delehedde M, Devenyns L, Maurage CA, Vivès RR. Endocan in cancers: a lesson from a circulating dermatan sulfate proteoglycan. Int J Cell Biol. 2013;2013:705027. doi:10.1155/2013/705027.

Yang J, Yang Q, Yu S, Zhang X. Endocan: A new marker for cancer and a target for cancer therapy. Biomed Rep. 2015 May;3(3):279-283. doi:10.3892/br.2015.438.

Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med. 1994 Nov;97(5):418-28. doi:10.1016/0002-9343(94)90321-2.

Soares P, Celestino R, Melo M, Fonseca E, Sobrinho-Simões M. Prognostic biomarkers in thyroid cancer. Virchows Arch. 2014 Mar;464(3):333-46. doi:10.1007/s00428-013-1521-2.

Shi Y, Su C, Hu H,et al. Serum MMP-2 as a potential predictive marker for papillary thyroid carcinoma. PLoS One. 2018 Jun 27;13(6):e0198896. doi:10.1371/journal.pone.0198896.

Zarkesh M, Zadeh-Vakili A, Akbarzadeh M, Fanaei SA, Hedayati M, Azizi F. The role of matrix metalloproteinase-9 as a prognostic biomarker in papillary thyroid cancer. BMC Cancer. 2018 Dec 3;18(1):1199. doi:10.1186/s12885-018-5112-0.

Lassalle P, Molet S, Janin A, et al. ESM-1 is a novel human endothelial cell-specific molecule expressed in lung and regulated by cytokines. J Biol Chem. 1996 Aug 23;271(34):20458-64. doi:10.1074/jbc.271.34.20458.

Tímár J, Lapis K, Dudás J, Sebestyén A, Kopper L, Kovalszky I. Proteoglycans and tumor progression: Janus-faced molecules with contradictory functions in cancer. Semin Cancer Biol. 2002 Jun;12(3):173-86. doi:10.1016/S1044-579X(02)00021-4.

Delehedde M, Lortat-Jacob H, Gallagher JT, et al. Proteoglycan involvement in inflammatory diseases. New developments in GAG-based therapies. Medicinal Chemistry Reviews-Online. 2005;2(4):345-357. doi:10.2174/1567203054637560.

Scherpereel A, Gentina T, Grigoriu B, et al. Overexpression of endocan induces tumor formation. Cancer Res. 2003 Sep 15;63(18):6084-6089.

Chen LY, Liu X, Wang SL, Qin CY. Over-expression of the Endocan gene in endothelial cells from hepatocellular carcinoma is associated with angiogenesis and tumour invasion. J Int Med Res. 2010 Mar-Apr;38(2):498-510. doi:10.1177/147323001003800213.

Kang YH, Ji NY, Han SR, et al. ESM-1 regulates cell growth and metastatic process through activation of NF-κB in colorectal cancer. Cell Signal. 2012 Oct;24(10):1940-9. doi:10.1016/j.cellsig.2012.06.004.

Liu N, Zhang LH, Du H, et al. Overexpression of endothelial cell specific molecule-1 (ESM-1) in gastric cancer. Ann Surg Oncol. 2010 Oct;17(10):2628-39. doi:10.1245/s10434-010-1037-9.

Béchard D, Scherpereel A, Hammad H, et al. Human endothelial-cell specific molecule-1 binds directly to the integrin CD11a/CD18 (LFA-1) and blocks binding to intercellular adhesion molecule-1. J Immunol. 2001 Sep 15;167(6):3099-106. doi:10.4049/jimmunol.167.6.3099.

Arpaci D, Karakece E, Tocoglu AG, et al. Endocan, TGF-beta, and ADMA as Risk Factors for Endothelial Dysfunction and Possible Vascular Disease in Patients with Subclinical Hypothyroidism. Ann Clin Lab Sci. 2016 Dec;46(6):601-607.

Shibuya M, Claesson-Welsh L. Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis. Exp Cell Res. 2006 Mar 10;312(5):549-60. doi:10.1016/j.yexcr.2005.11.012.

Klein M, Vignaud JM, Hennequin V, et al. Increased expression of the vascular endothelial growth factor is a pejorative prognosis marker in papillary thyroid carcinoma. J Clin Endocrinol Metab. 2001 Feb;86(2):656-8. doi:10.1210/jcem.86.2.7226.

Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev. 1997 Feb;18(1):4-25. doi:10.1210/edrv.18.1.0287.

Lennard CM, Patel A, Wilson J, Reinhardt B, Tuman C, Fenton C, Blair E, Francis GL, Tuttle RM. Intensity of vascular endothelial growth factor expression is associated with increased risk of recurrence and decreased disease-free survival in papillary thyroid cancer. Surgery. 2001 May;129(5):552-8. doi:10.1067/msy.2001.112592.

Kilicarslan AB, Ogus M, Arici C, Pestereli HE, Cakir M, Karpuzoglu G. Clinical importance of vascular endothelial growth factor (VEGF) for papillary thyroid carcinomas. APMIS. 2003 Mar;111(3):439-43. doi:10.1034/j.1600-0463.2003.t01-1-1110209.x.

Karaca Z, Tanriverdi F, Unluhizarci K, et al. VEGFR1 expression is related to lymph node metastasis and serum VEGF may be a marker of progression in the follow-up of patients with differentiated thyroid carcinoma. Eur J Endocrinol. 2011 Feb;164(2):277-84. doi:10.1530/EJE-10-0967.

Mohamad Pakarul Razy NH, Wan Abdul Rahman WF, Win TT. Expression of Vascular Endothelial Growth Factor and Its Receptors in Thyroid Nodular Hyperplasia and Papillary Thyroid Carcinoma: A Tertiary Health Care Centre Based Study. Asian Pac J Cancer Prev. 2019 Jan 25;20(1):277-282. doi:10.31557/APJCP.2019.20.1.277.




How to Cite

Peynirci, H., Ersoy, C., Sisman, P., Saraydaroglu, O., Demirtas, C. O., & Gul, O. O. (2021). Can metastasis and recurrence be detected with Endocan and Vascular Endothelial Growth Factor in thyroid papillary cancer?. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), 16(6), 496–501.



Original Researches