Determination of galectin-3, hepsin and thyroid transcription factor-1 levels in thyroid cancer patients; A prospective case-control study

Abstract

Aim:We aimed to evaluate the usage of Galectin-3, Hepsin andTTF-1 levels as a marker for the differentiation of malignant and benign in patients with thyroid nodules.

Metods:Study was done prospectively between January 2018 and April 2018 in the our clinic, in patients planned for operation due to thyroid nodule. Galectin-3, Hepsin andTTF-1 levels were measured in the pre-operative serum of the benign and malign groups. The measured levels are evaluated statistically to determine whether there was any significant difference between malignant and benign groups.

Results:When the levels of Galectin-3, Hepsin andTTF-1 in the malign and benign group were compared; There was a statistically significant difference inTTF-1 levels(p = .038), no significant difference was found in Hepsin and Galectin-3. When the macropapillary and micropapillary types were compared in the malign patient group, there was a significant difference between the Galectin-3 levels(p = .009), but no difference was found between Hepsin andTTF-1.

Conclusions:It was seen that the decrease of Galectin-3 level in thyroid papillary carcinoma could be effective in transformation from micro carcinoma to macro carcinoma, andTTF-1 could be an important marker at the differentiation between benign and  malign in thyroid nodules

Keywords

• Galectin-3,Hepsin,TTF-1,Thyroid malignancy

References

1. 1. Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA otolaryngology-- head & neck surgery. 2014 Apr;140(4):317-22.
2. 2. Ogilvie JB, Piatigorsky EJ, Clark OH. Current status of fine needle aspiration for thyroid nodules. Advances in surgery. 2006;40:223-38.
3. 3. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA: a cancer journal for clinicians. 2012 Jan-Feb;62(1):10-29.
4. 4. Brito JP, Yarur AJ, Prokop LJ, McIver B, Murad MH, Montori VM. Prevalence of thyroid cancer in multinodular goiter versus single nodule: a systematic review and meta-analysis. Thyroid : official journal of the American Thyroid Association. 2013 Apr;23(4):449-55.
5. 5. Liu FT, Rabinovich GA. Galectins as modulators of tumour progression. Nature reviews Cancer. 2005 Jan;5(1):29-41.
6. 6. Krzeslak A, Lipinska A. Galectin-3 as a multifunctional protein. Cellular & molecular biology letters. 2004;9(2):305-28.
7. 7. Sanabria A, Carvalho AL, Piana de Andrade V, Pablo Rodrigo J, Vartanian JG, Rinaldo A, et al. Is galectin-3 a good method for the detection of malignancy in patients with thyroid nodules and a cytologic diagnosis of "follicular neoplasm"? A critical appraisal of the evidence. Head & neck. 2007 Nov;29(11):1046-54. 8. Torres-Rosado A, O'Shea KS, Tsuji A, Chou S.H, Kurachi K. Hepsin, a putative cell-surface serine protease, is required for mammalian cell growth. Proceedings of the National Academy of Sciences of the United States of America. 1993 Aug 1;90(15):7181-5.
8. 9. Tripathi M, Nandana S, Yamashita H, Ganesan R, Kirchhofer D, Quaranta V. Laminin-332 is a substrate for hepsin, a protease associated with prostate cancer progression. The Journal of biological chemistry. 2008 Nov 7;283(45):30576-84.

9. 10. Vu TK, Liu RW, Haaksma CJ, Tomasek J.J, Howard E.W. Identification and cloning of the membrane-associated serine protease, hepsin, from mouse preimplantation embryos. The Journal of biological chemistry. 1997 Dec 12;272(50):31315-20.
10. 11. Netzel-Arnett S, Hooper JD, Szabo R, et al. Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer. Cancer metastasis reviews. 2003 Jun-Sep;22(2-3):237-58.
11. 12. Guazzi S, Price M, De Felice M, Madison EL, Quigley JP, Bugge TH, et al. Thyroid nuclear factor 1 (TTF-1) contains a homeodomain and displays a novel DNA binding specificity. The EMBO journal. 1990 Nov;9(11):3631-9.
12. 13. Kimura S, Hara Y, Pineau T, Fernandez-Salguero P, Fox CH, Ward JM, et al. The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. Genes & development. 1996 Jan 1;10(1):60-9.
13. 14. Barletta JA, Perner S, Iafrate AJ, Yeap BY, Weir BA, Johnson LA, et al. Clinical significance of TTF-1 protein expression and TTF-1 gene amplification in lung adenocarcinoma. Journal of cellular and molecular medicine. 2009 Aug;13(8b):1977-86.
14. 15. Myong NH. Thyroid transcription factor-1 (TTF-1) expression in human lung carcinomas: its prognostic implication and relationship with wxpressions of p53 and Ki-67 proteins. Journal of Korean medical science. 2003 Aug;18(4):494-500.
15. 16. Danese D, Sciacchitano S, Farsetti A, Andreoli M, Pontecorvi A. Diagnostic accuracy of conventional versus sonography-guided fine-needle aspiration biopsy of thyroid nodules. Thyroid : official journal of the American Thyroid Association. 1998 Jan;8(1):15-21.
16. 17. Bartolazzi A, Gasbarri A, Papotti M, Bussolati G, Lucante T, Khan A, et al. Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet (London, England). 2001 May 26;357(9269):1644-50.
17. 18. Orlandi F, Saggiorato E, Pivano G, Puligheddu B, Termine A, Cappia S, et al. Galectin-3 is a presurgical marker of human thyroid carcinoma. Cancer research. 1998 Jul 15;58(14):3015-20.
18. 19. Herrmann ME, LiVolsi VA, Pasha TL, Roberts SA, Wojcik EM, Baloch ZW. Immunohistochemical expression of galectin-3 in benign and malignant thyroid lesions. Archives of pathology & laboratory medicine. 2002 Jun;126(6):710-3.
19. 20. De Matos PS, Ferreira AP, de Oliveira Facuri F, Assumpção LV, Metze K, Ward LS. Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy. Histopathology. 2005 Oct;47(4):391-401.
20. 21. De Matos LL, Del Giglio AB, Matsubayashi CO, de Lima Farah M, Del Giglio A, da Silva Pinhal MA. Expression of CK-19, galectin-3 and HBME-1 in the differentiation of thyroid lesions: systematic review and diagnostic meta-analysis. Diagnostic pathology. 2012 Aug 13;7:97.
21. 22. Kawachi K, Matsushita Y, Yonezawa S, Nakano S, Shirao K, Natsugoe S, et al. Galectin-3 expression in various thyroid neoplasms and its possible role in metastasis formation. Human pathology. 2000 Apr;31(4):428-33.
22. 23. Leytus SP, Loeb KR, Hagen FS, Kurachi K, Davie EW. A novel trypsin-like serine protease (hepsin) with a putative transmembrane domain expressed by human liver and hepatoma cells. Biochemistry. 1988 Feb 9;27(3):1067-74.
23. 24. Kazama Y, Hamamoto T, Foster DC, Kisiel W. Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation. The Journal of biological chemistry. 1995 Jan 6;270(1):66-72.
24. 25. Stephan C, Yousef GM, Scorilas A, Jung K, Jung M, Kristiansen G, et al. Hepsin is highly over expressed in and a new candidate for a prognostic indicator in prostate cancer. The Journal of urology. 2004 Jan;171(1):187-91.
25. 26. Xing P, Li JG, Jin F, Zhao TT, Liu Q, Dong HT, et al. Clinical and biological significance of hepsin overexpression in breast cancer. Journal of investigative medicine : the official publication of the American Federation for Clinical Research. 2011 Jun;59(5):803-10.
26. 27. El-Rebey HS, Kandil MA, Samaka RM, Al-Sharaky DR, El Deeb K. The Role of Hepsin in Endometrial Carcinoma. Applied immunohistochemistry & molecular morphology : AIMM. 2017 Oct;25(9):624-631.
27. 28. Tanimoto H, Yan Y, Clarke J, Korourian S, Shigemasa K, Parmley TH, et al. Hepsin, a cell surface serine protease identified in hepatoma cells, is overexpressed in ovarian cancer. Cancer research. 1997 Jul 15;57(14):2884-7.
28. 29. Zhang M, Zhao J, Tang W, Wang Y3, Peng P1, Li L1, et al. High Hepsin expression predicts poor prognosis in Gastric Cancer. Scientific reports. 2016 Nov 14;6:36902.
29. 30. Kimura S. Thyroid-specific transcription factors and their roles in thyroid cancer. Journal of thyroid research. 2011;2011:710213.
30. 31. Stenhouse G, Fyfe N, King G, Chapman A, Kerr KM. Thyroid transcription factor 1 in pulmonary adenocarcinoma. Journal of clinical pathology. 2004 Apr;57(4):383-7.
31. 32. Anagnostou VK, Syrigos KN, Bepler G, Homer RJ, Rimm DL. Thyroid transcription factor 1 is an independent prognostic factor for patients with stage I lung adenocarcinoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2009 Jan 10;27(2):271-8.
32. 33. Fenton CL, Patel A, Burch HB, Tuttle RM, Francis GL. Nuclear localization of thyroid transcription factor-1 correlates with serum thyrotropin activity and may be increased in differentiated thyroid carcinomas with aggressive clinical course. Annals of clinical and laboratory science. 2001 Jul;31(3):245-52.
33. 34. Katoh R, Kawaoi A, Miyagi E, Li X, Suzuki K, Nakamura Y, et al. Thyroid transcription factor-1 in normal, hyperplastic, and neoplastic follicular thyroid cells examined by immunohistochemistry and nonradioactive in situ hybridization. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2000 May;13(5):570-6.
34. 35. Nonaka D, Tang Y, Chiriboga L, Rivera M, Ghossein R. Diagnostic utility of thyroid transcription factors Pax8 and TTF-2 (FoxE1) in thyroid epithelial neoplasms. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2008 Feb;21(2):192-200.