Possibilities traditional and liquid-based cytology combined with immunocytochemical detection of some molecular markers in the preoperative diagnosis of well-differentiated thyroid cancer

Aim. To establish the diagnostic value of liquid and traditional cytological diagnosis with immunocytochemical (ICC) detection proteins (galectin-3, nucleophosmin, Ki-67) in the preoperative diagnosis of well-differentiated thyroid cancer and analysis of the effect of the autoimmune process in the thyroid gland in the diagnostic accuracy.

Materials and methods. The traditional liquid-based cytology was performed on 107 samples and immunocytochemistry performed on 56 samples with histological findings: colloid goiter in 24 cases, 4 cases of Hashimoto’s thyroiditis, 4 cases of follicular adenoma, 22 cases of papillary cancer.

Results. The results of a comparison of cytological and histological findings. The results of studies of diagnostic accuracy expression of galectin-3, nucleophosmin, Ki-67 for the diagnosis of thyroid cancer. A formula was developed to help determine the presence of malignancy in thyroid with high accuracy.

Conclusion. The diagnostic accuracy of the method of liquid-based cytology is higher than the traditional method of cytology. ICC expression of Ki-67 method has 81.8% of sensitivity and 100% of specificity for the preoperative diagnosis of thyroid cancer. Conjoint definition HS Ki-67 and liquid-based cytology increases the sensitivity and specificity of the diagnosis of well-differentiated thyroid cancer preoperative to 100%. There no detected relations between the expression of galectin-3, NFM, Ki-67 and the presence an autoimmune process in the thyroid.

1. Состояние онкологической помощи населению России в 2014 году. / Под ред. Каприна А.Д., Старинского В.В., Петровой Г.В. М.: МНИОИ им. П.А. Герцена; 2015. [Kaprin AD, Starinskiy VV, Petrova GV, editors. Sostoyanie onkologicheskoy pomoshchi naseleniyu Rossii v 2014 godu. Moscow; 2015. (In Russ).]

2. Bartolazzi A, Orlandi F, Saggiorato E, et al. Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules within determinate fine-needle aspiration cytology: a prospective multicentre study. Lancet Oncol.2008;9(6):508-510. doi: 10.1016/S1470-2045(08)70132-3.

3. Knauf JA, Fagin JA. Role of MAPK pathway oncoproteins in thyroid cancer pathogenesis and as drug targets. Current Opinion in Cell Biology. 2009;21(2):296-303. doi: 10.1016/j.ceb.2009.01.013.

4. Kopczynska E, Junik R, Tyrakowski T. BRAF gene mutation in thyroid cancer. Pol Merkur Lekarski. 2006;20(116):210-213. doi: 10.1677/erc.1.0978.

5. Sethi K, Sarkar S, Das S, et al. Biomarkers for the diagnosis of thyroid cancer. J Experimental Therapeutics and Oncology. 2010; 8(4):341-352.

6. Raggio E, Camandona M, Solerio D, et al. The diagnostic accuracy of the immunocytochemical markers in the pre-operative evaluation of follicular thyroid lesions. J Endocrinol Invest. 2010;33(6):378-381. doi: 10.3275/6444.

7. Martins L, Matsuo SE, Ebina KN, et al. Galectin3 messenger ribonucleic acid and protein are expressed in benign thyroid tumors. J Clin Endocrinol Metab. 2002;87(10):4806-4810.

8. Патент РФ на изобретение № 2546011/ 10.04.2015. Бюл. № 10. Олиферова О.С., Кналян С.В., Трынов Н.Н., и др. Способ диагностики высокодифференцированного рака щитовидной железы. [Patent RUS №2546011/ 10.04.2015. Byul. №10. Oliferova OS, Knaljan SV, Trynov NN. A method for diagnosing highly differentiated thyroid cancer. (In Russ).]

9. Коган Е.А., Петунина Н.А., Чернышова Т.В., Лукьянченко Д.В. Определение экспрессии галектина-3 в ткани фолликулярных опухолей щитовидной железы // Клиническая и экспериментальная тиреоидология. – 2011. – Т. 7. – №1. – С. 45–49. [Kogan EA, Petunina NA, Chernyshova TV, Lukyanchenko DV. Determination of galectin-3 expression in the tissue of follicular thyroid tumors. Clinical and experimental thyroidology. 2011;7(1): 45-49. (In Russ).] doi: 10.14341/ket20117145-49.

10. Chui MH, Cassol CA, Asa SL, Mete O. Follicular epithelial dysplasia of the thyroid: morphological and immunohistochemical characterization of a putative preneoplastic lesion to papillary thyroid carcinoma in chronic lymphocytocthyroiditis. Virchows Arch. 2013;462(5):557-563. doi: 10.1007/s00428-013-1397-1.

11. Das DK, Khanna CM, Tripathi RP, et al. Solitary nodular goiter. Review of cytomorphologic features in 441 cases. Acta Cytol. 1999;43(4):563-572.

12. Choudhury M, Singh S, Agarwal S. Diagnostic utility of Ki67 and p53 immunostaining on solitary thyroid nodule – a cytohistological and radionuclide scintigraphic study. Indian J Pathol Microbiol. 2011;54(3):472-475. doi: 10.4103/0377-4929.85077.

13. Dinets A, Hulchiy M, Sofiadis A, et al. Clinical, genetic, and immunohistochemical characterization of 70 Ukrainian adult cases with post-Chernobyl papillary thyroid carcinoma. Eur J Endocrinol. 2012;166(6):1049-1060. doi: 10.1530/EJE-12-0144.

14. Pujani M, Arora B, Pujani M, et al. Role of Ki-67 as a proliferative marker in lesions of thyroid. Indian J Cancer. 2010;47(3):304-307. doi: 10.4103/0019-509X.

15. Бондаренко О.О., Шпонька И.С., Гриценко П.А. Использование онкомаркеров в морфологической диагностике эпителиальных опухолей щитовидной железы. // Морфологiя. – 2010. – Т. 3. – №2 – С. 12–16. [Bondarenko OO,Shponka ІS, Gricenko PA. Using of oncomarkers in morphological diagnostics of epithelial tumors of thyroid gland. Morfologija. 2010;3(2):12-16. (In Russ).]

16. Aiad HA, Bashandy MA, Abdou AG, Zahran AA. Significance of AgNORs and ki-67 proliferative markers in differential diagnosis of thyroid lesions. Pathol Oncol Res. 2013;19(2):167-175. doi: 10.1007/s12253-012-9565-1.

17. Свиридова Т.Е., Коган Е.А., Пальцев М.А., Середин В.П. Гистологические и молекулярно-генетические маркеры злокачественности в различных вариантах папиллярного рака щитовидной железы. Архив патологии. – 2002. – Т. 6. – С. 19–23. [Sviridova TE, Kogan EA, Palcev MA, Seredin VP. The histological and molecular genetic markers of malignancy in various variants of papillary thyroid cancer. Arhiv patologii. 2002;6:19-23. (In Russ).]

18. Пальцев М.А., Коган Е.А., Тунцова О.И. Иммуногистохимия биомолекулярных маркеров раннего рака щитовидной железы. Архив патологии. – 1997. – Т. 6. – С. 18–23. [Palcev MA, Kogan EA, Tuncova OI.Immunohistochemistry biomolecular markers of early thyroid cancer. Arhiv patologii. 1997;6:18-23. (In Russ).]

19. Цыган В.Н., Казаков С.П., Заботина Т.Н., Кушлинский Н.Е. Маркеры апоптоза и пролиферации у больных с онкологическими и аутоиммунными заболеваниями щитовидной железы. // Вестник Российской военно-медицинской академии. – 2010. – Т. 32. – №4 – С. 197–204. [Cygan VN, Kazakov SP, Zabotina TN, Kushlinskij NE. Proliferation and apoptosis markers in patients with cancer and autoimmune thyroid diseases. Vestnik Rossijskoj voenno-medicinskoj akademii. 2010; 32(4):197-204. (In Russ).]

20. Song Q, Wang D, Lou Y, et al. Diagnostic significance of CK19, TG, Ki67 and galectin-3 expression for papillary thyroid carcinoma in the northeastern region of China. Diagn Pathol. 2011;126(6). doi: 10.1186/1746-1596-6-126.

21. Боташева В.С., Калоева А.А., Эркенова Л.Д. Оценка пролиферативной активности тиреоцитов при узловом зобе. Фундаментальные исследования. – 2015. – №1 – С. 699–703. [Botasheva VS, Kaloeva AA, Jerkenova LD.Rating of proliferative of thyrocytes in nodular goiter. Fundamentalnye issledovanija. 2015;1:699-703. (In Russ).]

22. Szebeni A, Mehrotra В, Baumann A, et al. Nucleolar protein B23 stimulates nuclear import of the HIV-1 Rev protein and NLS-conjugated albumin. Biochemistry. 1997;36(13):3941-3949.

23. Pianta A, Puppin C, Passon N, et al. Nucleophosmin delocalization in thyroid tumour cells. Endocr Pathol. 2011;22(1):18-23. doi: 10.1007/s12022-011-9147-x.

24. Бельцевич Д.Г., Ванушко В.Э., Мельниченко Г.А., и др. ПРОЕКТ: Клинические рекомендации Российской ассоциации эндокринологов по диагностике и лечению узлового зоба (новая редакция 2015 года). Эндокринная хирургия. – 2015. – №1 – С. 15–21. [Bel’cevich DG, Vanushko VJ, Melnichenko GA, et al. DRAFT: Russian Association of Endocrinologists Clinic Guidelines for Thyroid Nodules Diagnostic and Treatment. Endocine Surgery. 2015;1:15-21. (In Russ.).] doi: 10.14341/serg2015115-21.

25. Саприна Т.В., Прохоренко Т.С., Резцова В.М., и др. Особенности продукции и рецепции цитокинов Th1/Th2 профиля при болезни Грейвса. Клиническая и экспериментальная тиреоидология. – 2012. – Т. 8. – №2 – С. 43–49.[Saprina TV, Prohorenko TS, Rezcova VM, et al. Th1/Th2 cytokine production and reception features in Graves’ disease. Clinical and Experimental Thyroidology. 2012;8(2):43-49. (In Russ).] doi:10.14341/ket20128243-49.

26. Волченко Н.Н., Славнова Е.Н., Тугулукова А.А. Жидкостная цитология в онкологии. Онкология. – 2013. – Т.1. – №5 – С. 26–31. [Volchenko NN, Slavnova EN, Tugulukova AA. Liquid-based cytology in oncology. Onkologija.2013;1(5):26-31.(In Russ).

27. Брынова О.В., Касоян К.Т., Шабалова И.П. и др. Метод жидкостной цитологии в диагностике заболеваний щитовидной железы. // Клиническая лабораторная диагностика. - 2016. - Т. 61. - № 4. - С. 225-228. [Brynova O.V.,Kasoyan K.T., Shabalova I.P., et. al. The technique of fluid cytology in diagnostic of thyroid diseases. // Klinichescheskaya Laboratornaya Diagnostika. 2016;61(4):225-228. (In Russ).] doi:10.18821/0869-2084-2016-61-4-225-228.]