endosergЭндокринная хирургияEndocrine Surgery2306-35132310-3965Типография «Печатных дел Мастер»10.14341/2306-3513-2012-2-15-20endoserg-3999Research ArticleСтатьиArticlesАутоантительные биомаркеры в дифференциальной диагностике фолликулярных опухолей щитовидной железыAutoantibody profiling of benign and malignant thyroid tumors and design of a prototype diagnostic arrayLanshchakovK Vk.lanshakov@mail.ruBelousovP V-VanushkoV E-AbrosimovA Yu-KuprashD V-KuznetsovN S-20121506201262№2 (2012)1520Copyright © Lanshchakov K.V., Belousov P.V., Vanushko V.E., Abrosimov A.Y., Kuprash D.V., Kuznetsov N.S., 20122012Lanshchakov K.V., Belousov P.V., Vanushko V.E., Abrosimov A.Y., Kuprash D.V., Kuznetsov N.S.Lanshchakov K.V., Belousov P.V., Vanushko V.E., Abrosimov A.Y., Kuprash D.V., Kuznetsov N.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.surg-endojournals.ru/jour/article/view/3999

На сегодняшний день “золотым стандартом” в диагностике опухолей щитовидной железы (ЩЖ) является тонкоигольная аспирационная биопсия (ТАБ). Однако ТАБ в 15–30% наблюдений не позволяет дифференцировать доброкачественную природу опухоли от злокачественной. В целях поиска дополнительных индикаторов в предоперационной дифференциальной диагностике опухолей ЩЖ нами исследован диагностический потенциал 3 кандидатных раковоассоциированных антигенов в клинической группе 22 доброкачественных и 26 злокачественных опухолей ЩЖ. Чувствительность и специфичность метода составили 55–60 и 95–100% соответственно ( p < 0,001, точный критерий Фишера). Таким образом, была разработана прототипная панель антигенов для дифференциальной диагностики опухолей ЩЖ, которую можно рассматривать как платформу для дальнейших разработок с целью повышения точности предоперационной диагностики рака ЩЖ.

Currently the “gold standard” in diagnostics of thyroid tumors is a fine-needle aspiration cytology (FNAC). However, FNAC cannot discriminate between benign and malignant thyroid tumors in 15 to 30% of observations. In order to develop an additional tool for differential diagnostics of thyroid tumors we evaluated the diagnostic performance of 3-antigen serum autoantibody signature in groups of benign ( n = 22) and malignant ( n = 26) thyroid tumors using a dot-blot ELISA-based analysis The sensitivity and specificity of resultant array were estimated to be 55–60% and 95–100%, respectively ( p < 0.001 according to one-sided Fisher Exact Test). Thus, we created a prototype antigen array for differential diagnostics of thyroid tumors which can be regarded as a platform for design of more complicated panel, highly sensitive in thyroid cancer detection, which can significantly improve the accuracy of preoperative diagnosis of thyroid cancer.

фолликулярная опухольрак щитовидной железыаутоантительные биомаркерытонкоигольная пункционная биопсияfollicular neoplasmthyroid cancercancer-associated antigensfine-needleReferencesAdeniran A.J., Zhu Z., Gandhi M. et. al. Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. Am. J. Surg. Pathol. 2006; 30 (2): 216–222.Adeniran A.J., Zhu Z., Gandhi M. et. al. Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. Am. J. Surg. Pathol. 2006; 30 (2): 216–222.Au A.Y., McBride C., Wilhelm K.G. Jr. et. al. PAX8-peroxisome proliferator-activated receptor gamma (PPARgamma) disrupts normal PAX8 or PPARgamma transcriptional function and stimulates follicular thyroid cell growth. Endocrinology 2006;147 (1): 367–376.Au A.Y., McBride C., Wilhelm K.G. Jr. et. al. PAX8-peroxisome proliferator-activated receptor gamma (PPARgamma) disrupts normal PAX8 or PPARgamma transcriptional function and stimulates follicular thyroid cell growth. Endocrinology 2006;147 (1): 367–376.Begum S., Rosenbaum E., Henrique R. et. al. BRAF mutations in anaplastic thyroid carcinoma: implications for tumor origin, diagnosis and treatment. Mod. Pathol. 2004; 17 (11): 1359–1363.Begum S., Rosenbaum E., Henrique R. et. al. BRAF mutations in anaplastic thyroid carcinoma: implications for tumor origin, diagnosis and treatment. Mod. Pathol. 2004; 17 (11): 1359–1363.Brown L.M. et. al. Quantitative and qualitative differences in protein expression between papillary thyroid carcinoma and normal thyroid tissue. Mol. Carcinog. 2006; 45. (8): 613–626.Brown L.M. et. al. Quantitative and qualitative differences in protein expression between papillary thyroid carcinoma and normal thyroid tissue. Mol. Carcinog. 2006; 45. (8): 613–626.Cakir M., Grossman A.B. Medullary thyroid cancer: molecular biology and novel molecular therapies. Neuroendocrinology 2009; 90 (4): 323–348.Cakir M., Grossman A.B. Medullary thyroid cancer: molecular biology and novel molecular therapies. Neuroendocrinology 2009; 90 (4): 323–348.Cap J., Ryska A., Rehorkova P. et. al. Sensitivity and specificity of the fine needle aspiration biopsy of the thyroid: clinical point of view. Clin. Endocrinol. (Oxf.) 1999; 51, 509–515.Cap J., Ryska A., Rehorkova P. et. al. Sensitivity and specificity of the fine needle aspiration biopsy of the thyroid: clinical point of view. Clin. Endocrinol. (Oxf.) 1999; 51, 509–515.Chiappetta G., Toti P., Cetta F. et. al. The RET/PTC oncogene is frequently activated in oncocytic thyroid tumors (Hurthle cell adenomas and carcinomas), but not in oncocytic hyperplastic lesions. J. Clin. Endocrinol. Metab. 2002; 87 (1): 364–369.Chiappetta G., Toti P., Cetta F. et. al. The RET/PTC oncogene is frequently activated in oncocytic thyroid tumors (Hurthle cell adenomas and carcinomas), but not in oncocytic hyperplastic lesions. J. Clin. Endocrinol. Metab. 2002; 87 (1): 364–369.Ciampi R., Nikiforov Y.E. RET/PTC rearrangements and BRAF mutations in thyroid tumorigenesis. Endocrinology 2007; 148 (3): 936–941.Ciampi R., Nikiforov Y.E. RET/PTC rearrangements and BRAF mutations in thyroid tumorigenesis. Endocrinology 2007; 148 (3): 936–941.Ciampi R., Giordano T.J., Wikenheiser-Brokamp K. et. al. HOOK3-RET: a novel type of RET/PTC rearrangement in papillary thyroid carcinoma. Endocr. Relat. Cancer 2007; 14 (2): 445–452.Ciampi R., Giordano T.J., Wikenheiser-Brokamp K. et. al. HOOK3-RET: a novel type of RET/PTC rearrangement in papillary thyroid carcinoma. Endocr. Relat. Cancer 2007; 14 (2): 445–452.Ciampi R., Knauf J.A., Kerler R. et. al. Oncogenic AKAP9BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer. J. Clin. Invest. 2005; 115 (1): 94–101.Ciampi R., Knauf J.A., Kerler R. et. al. Oncogenic AKAP9BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer. J. Clin. Invest. 2005; 115 (1): 94–101.Du Villard J.A., Schlumberger M., Wicker R. et. al. Role of ras and gsp oncogenes in human epithelial thyroid tumorigenesis. J. Endocrinol. Invest. 1995; 18 (2):124–126.Du Villard J.A., Schlumberger M., Wicker R. et. al. Role of ras and gsp oncogenes in human epithelial thyroid tumorigenesis. J. Endocrinol. Invest. 1995; 18 (2):124–126.Fagin J.A., Mitsiades N. Molecular pathology of thyroid cancer: diagnostic and clinical implications. Best Pract Res Clin. Endocrinol. Metab. 2008; 22 (6): 955–969.Fagin J.A., Mitsiades N. Molecular pathology of thyroid cancer: diagnostic and clinical implications. Best Pract Res Clin. Endocrinol. Metab. 2008; 22 (6): 955–969.Fan Y., Shi L., Liu Q. et. al. Discovery and identification of potential biomarkers of papillary thyroid carcinoma. Mol. Cancer. 2009.Fan Y., Shi L., Liu Q. et. al. Discovery and identification of potential biomarkers of papillary thyroid carcinoma. Mol. Cancer. 2009.Ghossein R.A., Leboeuf R., Patel K.N. et. al. Tall cell variant of papillary thyroid carcinoma without extrathyroid extension: biologic behavior and clinical implications. Thyroid. 2007; 17, 655–661.Ghossein R.A., Leboeuf R., Patel K.N. et. al. Tall cell variant of papillary thyroid carcinoma without extrathyroid extension: biologic behavior and clinical implications. Thyroid. 2007; 17, 655–661.Greenspan F.S. The role of fine-needle aspiration biopsy in the management of palpable thyroid nodules. Am. J. Clin. Pathol. 1997; 108: S26–S30.Greenspan F.S. The role of fine-needle aspiration biopsy in the management of palpable thyroid nodules. Am. J. Clin. Pathol. 1997; 108: S26–S30.Greenlee R.T., Hill-Harmon M.B., Murray T., Thun M. Cancer statistics. CA Cancer J.Clin. 2001; 51, 15–36.Greenlee R.T., Hill-Harmon M.B., Murray T., Thun M. Cancer statistics. CA Cancer J.Clin. 2001; 51, 15–36.Gregory Powell J., Wang X., Allard B.L. et. al. The PAX8/ PPARgamma fusion oncoprotein transforms immortalized human thyrocytes through a mechanism probably involving wild-type PPARgamma inhibition. Oncogene. 2004; 23 (20): 3634–3641.Gregory Powell J., Wang X., Allard B.L. et. al. The PAX8/ PPARgamma fusion oncoprotein transforms immortalized human thyrocytes through a mechanism probably involving wild-type PPARgamma inhibition. Oncogene. 2004; 23 (20): 3634–3641.Hundahl S.A., Fleming I.D., Fremgen A.M., Menck H.R. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985–1995. Cancer 1998; 83: 2638–2648.Hundahl S.A., Fleming I.D., Fremgen A.M., Menck H.R. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985–1995. Cancer 1998; 83: 2638–2648.Johannes L. Bos. RAS oncogenes in human cancer: a review. Cancer Res. 1989; 49: 4682–4689.Johannes L. Bos. RAS oncogenes in human cancer: a review. Cancer Res. 1989; 49: 4682–4689.Kim J., Giuliano A.E., Turner R.R. et. al. Lymphatic mapping establishes the role of BRAF gene mutation in papillary thyroid carcinoma. Ann. Surg. 2006; 244 (5): 799–804.Kim J., Giuliano A.E., Turner R.R. et. al. Lymphatic mapping establishes the role of BRAF gene mutation in papillary thyroid carcinoma. Ann. Surg. 2006; 244 (5): 799–804.Kroll T.G., Sarraf P., Pecciarini L. et. al. PAX8-PPARgamma1 fusion oncogene in human thyroid thyroid carcinoma [corrected]. Science 2000; 289:1357–1360.Kroll T.G., Sarraf P., Pecciarini L. et. al. PAX8-PPARgamma1 fusion oncogene in human thyroid thyroid carcinoma [corrected]. Science 2000; 289:1357–1360.Lui W.O., Zeng L., Rehrmann V. et. al. CREB3L2-PPAR gamma fusion mutation identifies a thyroid signaling pathway regulated by intramembrane proteolysis. Cancer. Res. 2008;68 (17): 7156–7164.Lui W.O., Zeng L., Rehrmann V. et. al. CREB3L2-PPAR gamma fusion mutation identifies a thyroid signaling pathway regulated by intramembrane proteolysis. Cancer. Res. 2008;68 (17): 7156–7164.Netea-Maier R.T., Hunsucker S.W., Hoevenaars B.M. et. al. Discovery and Validation of Protein Abundance Differences between Follicular Thyroid Neoplasms. Cancer Research 2008; 68: 1572.Netea-Maier R.T., Hunsucker S.W., Hoevenaars B.M. et. al. Discovery and Validation of Protein Abundance Differences between Follicular Thyroid Neoplasms. Cancer Research 2008; 68: 1572.Nikiforov Y.E., Nikiforova M.N., Gnepp D.R., Fagin J.A. Prevalence of mutations of ras and p53 in benign and malignant thyroid tumors from children exposed to radiation after the Chernobyl nuclear accident. Oncogene. 1996; 13 (4): 687–693.Nikiforov Y.E., Nikiforova M.N., Gnepp D.R., Fagin J.A. Prevalence of mutations of ras and p53 in benign and malignant thyroid tumors from children exposed to radiation after the Chernobyl nuclear accident. Oncogene. 1996; 13 (4): 687–693.Nikiforova M.N., Kimura E.T., Gandhi M. et. al. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J. Clin. Endocrinol. Metab. 2003;88 (11): 5399–5404.Nikiforova M.N., Kimura E.T., Gandhi M. et. al. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J. Clin. Endocrinol. Metab. 2003;88 (11): 5399–5404.Nikiforov Y.E., Rowland J.M., Bove K.E. et al. Distinct pattern of ret oncogene rearrangements in morphological variants of radiation-induced and sporadic thyroid papillary carcinomas in children. Cancer Res. 1997; 57 (9): 1690–1694.Nikiforov Y.E., Rowland J.M., Bove K.E. et al. Distinct pattern of ret oncogene rearrangements in morphological variants of radiation-induced and sporadic thyroid papillary carcinomas in children. Cancer Res. 1997; 57 (9): 1690–1694.Pacini F., Schlumberger M., Dralle H. et. al. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur. J. Endocrinol. 2006;154: 787–803.Pacini F., Schlumberger M., Dralle H. et. al. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur. J. Endocrinol. 2006;154: 787–803.Pasca di Magliano M., Di Lauro R., Zannini M. Pax8 has a key role in thyroid cell differentiation. Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13144-9. carcinoma [corrected]. Science 2000; 289 (5483):1357–1360. Erratum in: Science 2000; 289 (5484): 1474.Pasca di Magliano M., Di Lauro R., Zannini M. Pax8 has a key role in thyroid cell differentiation. Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13144-9. carcinoma [corrected]. Science 2000; 289 (5483):1357–1360. Erratum in: Science 2000; 289 (5484): 1474.Placzkowski K.A., Reddi H.V., Grebe S.K. et. al. The Role of the PAX8/PPARgamma Fusion Oncogene in Thyroid Cancer. PPAR Res. 2008; 29: 672829.Placzkowski K.A., Reddi H.V., Grebe S.K. et. al. The Role of the PAX8/PPARgamma Fusion Oncogene in Thyroid Cancer. PPAR Res. 2008; 29: 672829.Reddi H.V., McIver B., Grebe S.K., Eberhardt N.L. The paired box-8/peroxisome proliferator-activated receptor-gamma oncogene in thyroid tumorigenesis. Endocrinology 2007; 148 (3): 932–935.Reddi H.V., McIver B., Grebe S.K., Eberhardt N.L. The paired box-8/peroxisome proliferator-activated receptor-gamma oncogene in thyroid tumorigenesis. Endocrinology 2007; 148 (3): 932–935.Riesco-Eizaguirre G., Gutierrez-Martinez P., Garcia-Cabezas M.A. et. al. The oncogene BRAF V600E is associated with a high risk ofrecurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na+/Itargeting to the membrane. Endocr. Relat. Cancer 2006; 13 (1): 257–269.Riesco-Eizaguirre G., Gutierrez-Martinez P., Garcia-Cabezas M.A. et. al. The oncogene BRAF V600E is associated with a high risk ofrecurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na+/Itargeting to the membrane. Endocr. Relat. Cancer 2006; 13 (1): 257–269.Saavedra H.I., Knauf J.A., Shirokawa J.M. et. al. The RAS oncogene induces genomic instability in thyroid PCCL3 cells via the MAPK pathway. Oncogene. 2000; 19 (34): 3948–3954.Saavedra H.I., Knauf J.A., Shirokawa J.M. et. al. The RAS oncogene induces genomic instability in thyroid PCCL3 cells via the MAPK pathway. Oncogene. 2000; 19 (34): 3948–3954.Saenko V., Rogounovitch T., Shimizu-Yoshida Y. et. al. Novel tumorigenic rearrangement, Delta rfp/ret, in a papillary thyroid carcinoma from externally irradiated patient. Mutat Res. 2003; 527 (1–2): 81–90.Saenko V., Rogounovitch T., Shimizu-Yoshida Y. et. al. Novel tumorigenic rearrangement, Delta rfp/ret, in a papillary thyroid carcinoma from externally irradiated patient. Mutat Res. 2003; 527 (1–2): 81–90.Salajegheh A., Petcu E.B., Smith R.A., Lam A.K. Follicular variant of papillary thyroid carcinoma: a diagnostic challenge for clinicians and pathologists. Postgrad. Med. J. 2008; 84: 78–82.Salajegheh A., Petcu E.B., Smith R.A., Lam A.K. Follicular variant of papillary thyroid carcinoma: a diagnostic challenge for clinicians and pathologists. Postgrad. Med. J. 2008; 84: 78–82.Santoro M., Papotti M., Chiappetta G. et. al. RET activation and clinicopathologic features in poorly differentiated thyroid tumors. J. Clin. Endocrinol. Metab. 2002; 87 (1): 370–379.Santoro M., Papotti M., Chiappetta G. et. al. RET activation and clinicopathologic features in poorly differentiated thyroid tumors. J. Clin. Endocrinol. Metab. 2002; 87 (1): 370–379.Suarez H.G. Genetic alterations in human epithelial thyroid tumours. Clin. Endocrinol. (Oxf.) 1998; 48 (5): 531–546.Suarez H.G. Genetic alterations in human epithelial thyroid tumours. Clin. Endocrinol. (Oxf.) 1998; 48 (5): 531–546.Trovisco V., Vieira de Castro I., Soares P. et. al. BRAF mutations are associ ated with some histological types of papillary thyroid carcinoma. J. Pathol. 2004; 202 (2): 247–251.Trovisco V., Vieira de Castro I., Soares P. et. al. BRAF mutations are associ ated with some histological types of papillary thyroid carcinoma. J. Pathol. 2004; 202 (2): 247–251.Wojciechowska K., Lewinski A. BRAF mutations in papillary thyroid carcinoma. Endocr Regul. 2006; 40 (4): 129–138.Wojciechowska K., Lewinski A. BRAF mutations in papillary thyroid carcinoma. Endocr Regul. 2006; 40 (4): 129–138.

The authors declare that there are no conflicts of interest present.