Mutlu ŞAHİN, Mehmet SAYDAM, Kerim YILMAZ, Hamdullah YANIK, İbrahim YILMAZ, Görkem GÜNDOĞAN, Cem AZILI, Melih AKINCI, Mehmet GÜLÇELİK

Serum endokan seviyeleri tiroid malignitesini tahmin edebilir: prospektif bir klinik çalışma

Amaç: Tiroidin iyi huylu ve kötü huylu hastalıklarının ayırıcı tanısı, biyopsi ile tanı konulmamış borderline malignite ve malignitelerde önemlidir. Bu çalışmada tiroid kanseri, nodüler guatr ve tiroiditli hastalarda endokan molekül düzeylerinin belirlenmesi amaçlanmıştır. Böylelikle tiroid hastalıklarının ayırıcı tanısında endokan molekülünün kullanılabilirliğinin belirlenmesi amaçlandı. Gereç ve Yöntem: Çalışma, 1 Mart 2018 ile 1 Ağustos 2018 tarihleri arasında gerçekleştirildi. Bu süre içerisinde tiroid hastalığı nedeniyle ameliyat planlanıp çalışmaya gönüllü olarak katılmak isteyen hastalar çalışmaya dahil edildi. Prospektif, kesitsel bir klinik çalışma tasarlandı. Çalışmaya dahil edilen hastalar patoloji raporu sonuçlarına göre dört gruba ayrıldı; Grup 1: Papiller tiroid kanseri (PTK), Grup 2: Tiroidit zemininde multinodüler guatr, Grup 3: Multinodüler guatr (MNG), Grup 4: Foliküler tiroid kanseri (FTK). Bulgular: Çalışmaya toplam 72 hasta dahil edildi. Dört grubu karşılaştıran çoklu analizde, gruplar arasında istatistiksel olarak anlamlı bir fark görülmedi (p> 0,050). Benign ve malign hasta grupları karşılaştırıldığında endokan düzeyleri malign grupta istatistiksel olarak anlamlı yüksek bulundu (p = 0,0375). Tiroid karsinom grupları kendi aralarında karşılaştırıldığında endokan düzeyinin FTK'nde PTK'ne göre daha yüksek olduğu tespit edildi (p = 0,047). Sonuç: Malign tiroid hastalıklarında “endokan” düzeyinin arttığı gözlendi. Bu özellikle hematojen yolla yayılım gösteren FTK'nde daha fazlaydı. Bu, "endokan" molekülünün genel bir tümör belirteci olarak kullanılabileceğine dair cesaret verici bir işarettir. Bununla birlikte, geniş randomize serilerle ileriye dönük ek çalışmalara ihtiyaç vardır.

Anahtar Kelimeler:

Tiroid karsinomu, tiroid nodülü, tiroidit, guatr

Serum endocan levels can predict malignancy of thyroid: a prospective clinical study

Aim: The differential diagnosis of benign and malignant diseases of the thyroid is important in borderline malignancies and malignancies that have not been diagnosed with biopsy. This study aimed to determine endocan molecule levels in patients with thyroid cancer, nodular goiter and thyroiditis. Thus, it was aimed to determine the availability of the endocan molecule in the differential diagnosis of thyroid diseases. Material and Method: The study was conducted between March 1, 2018 and August 1, 2018. During this period, patients who were scheduled for surgery due to thyroid disease and wanted to participate in the study voluntarily were included in the study. A prospective, cross-sectional clinical trial was designed. Patients included in the study were divided into four groups, according to their pathology report results; Group 1: Papillary thyroid cancer (PTC), Group 2: Multinodular goiter on thyroiditis background, Group 3: Multinodular goiter (MNG), Group 4: Follicular thyroid cancer (FTC). Results: A total of 72 patients were included in the study. Multiple analysis comparing the four groups, showed no statistically significant difference between the groups (p>0.050). When the benign and malignant patient groups were compared, endocan levels were found to be statistically significantly higher in the malignant group (p=0.0375). When thyroid carcinoma groups were compared among themselves, the endocan level was detected to be higher in FTC, compared to PTC (p=0.047). Conclusion: The level of “endocan” was observed to increase in malignant thyroid diseases. This was particularly so in FTC, which shows spreading via the hematogenous route. This is an encouraging sign that the "endocan" molecule can be used as a general tumor marker. However, prospective additional studies with large randomized series are needed.

Keywords:

Thyroid carcinoma, tiroid nodülü, thyroiditis, goiter,

PDF

___

1. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016 Jan. 26 (1):1-133.
2. Dogan L, Karaman N, Yilmaz KB, Ozaslan C, Atalay C. Total thyroidectomy for the surgical treatment of multinodular goiter. Surg Today. 2011 Mar;41(3):323-7.
3. Malloy, K.M. and M.F. Cunnane, Pathology and cytologic features of thyroid neoplasms. Surgical Oncology Clinics, 2008. 17(1): p. 57-70.
4. Lassalle P, Molet S, Janin A, Heyden JV, Tavernier J, Fiers W, 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.
5. Scherpereel A, Gentina T, Grigoriu B, Sénéchal S, Janin A, Tsicopoulos A, et al. Overexpression of endocan induces tumor formation. Cancer Res. 2003 Sep 15;63(18):6084-9.
6. Grigoriu BD, Depontieu F, Scherpereel A, Gourcerol D, Devos P, Ouatas T, et al. Endocan expression and relationship with survival in human non-small cell lung cancer. Clin Cancer Res. 2006 Aug 1;12(15):4575-82.
7. Sarrazin S, Maurage CA, Delmas D, Lassalle P, Delehedde M. Endocan as a Biomarker of Endothelial Dysfunction in Cancer. Journal of Science and Therapy, vol. 2, no. 2, pp47-52, 2010.
8. 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. Epub 2015 Feb 26.
9. Shin JW, Huggenberger R, Detmar M. Transcriptional profiling of VEGF-A and VEGF-C target genes in lymphatic endothelium reveals endothelial-specific molecule-1 as a novel mediator of lymphangiogenesis. Blood. 2008 Sep 15;112(6):2318-26. doi: 10.1182/blood-2008-05-156331. Epub 2008 Jul 9.
10. 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.
11. Lv Z, Fan Y, Chen H, Zhao D. Endothelial cell-specific molecule-1: a potential serum marker for gastric cancer. Tumour Biol. 2014;35(10): 10497–10502.
12. Liu N, Zhang LH, Du H, et al. Overexpression of endothelial cell specific molecule-1 (ESM-1) in gastric cancer. Ann Surg Oncol. 2010; 17(10):2628–2639.
13. Jiang H, Fu XG, Chen YT. Serum level of endothelial cell-specific molecule-1 and prognosis of colorectal cancer. Genet Mol Res. 2015; 14(2):5519–5526.
14. Kim JH, Park MY, Kim CN, 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. 2012;28(5):1701–1708.
15. Chang Y, Niu W, Lian PL, Wang XQ, Meng ZX, Liu Y, Zhao R. Endocan-expressing microvessel density as a prognostic factor for survival in human gastric cancer. World J Gastroenterol. 2016 Jun 21;22(23):5422-9. doi: 10.3748/wjg.v22.i23.5422.
16. Ji NY, Kim YH, Jang YJ, Kang YH, Lee CI, Kim JW, et al. Identification of endothelial cell-specific molecule-1 as a potential serum marker for colorectal cancer. Cancer Sci. 2010 Oct;101(10):2248-53. doi: 10.1111/j.1349-7006.2010.01665.x. Epub 2010 Jul 30.
17. Sagara A, Igarashi K, Otsuka M, Kodama A, Yamashita M, Sugiura R, et al. Endocan as a prognostic biomarker of triple-negative breast cancer. Breast Cancer Res Treat. 2017 Jan;161(2):269-278.
18. L. Zuo, S. M. Zhang, R. L. Hu et al., “Correlation between expression and diferentiation of endocan in colorectal cancer,” World Journal of Gastroenterology, vol. 14, no. 28, pp. 562– 4568, 2008.
19. Sarrazin S, Adam E, Lyon M, Depontieu F, et al. (2006). Endocan or endothelial cell specifc molecule-1 (ESM-1): a potential novel endothelial cell marker and a new target for cancer therapy. Biochim. Biophys. Acta 1765: 25-37.
20. Huang GW, Tao YM and Ding X (2009). Endocan expression correlated with poor survival in human hepatocellular carcinoma. Dig. Dis. Sci. 54: 389-394.
21. Maurage CA, Adam E, Mineo JF, Sarrazin S, et al. (2009). Endocan expression and localization in human glioblastomas. J. Neuropathol. Exp. Neurol. 68: 633-641.
22. Arpaci D, Karakece E, Tocoglu AG, Ergenc H, Gurol G, Ciftci IH, 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.
23. Gungor A, Palabiyik SS, Bayraktutan Z, Dursun H, Gokkaya N, Bilen A, et al. Levels of endothelial cell-specific molecule-1 (ESM-1) in overt hypothyroidisim. Endocr Res. 2016 Nov;41(4):275-280. Epub 2016 Feb 23.
24. Voiosu T, Bălănescu P, Benguş A, Voiosu A, Baicuş CR, Barbu M, Ladaru A, et al. Serum endocan levels are increased in patients with inflammatory bowel disease. Clin Lab. 2014;60(3):505-10.
25. 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. Epub 2013 Mar 28.