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Immunohistochemical Biomarkers in Thyroid Pathology

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Abstract

The application of immunohistochemistry to the diagnosis of thyroid lesions has increased as new biomarkers have emerged. In this review, we discuss the biomarkers that are critical for accurate diagnosis, prognosis, and management. Immunohistochemical markers are used to confirm that an unusual tumor in the thyroid is indeed of thyroid origin, either of follicular epithelial or C-cell differentiation; the various mimics include nonthyroidal lesions such as parathyroid tumors, paragangliomas, thymic neoplasms, and metastatic malignancies. Tumors of thyroid follicular epithelial cells can be further subclassified using a number of immunohistochemical biomarkers that can distinguish follicular-derived from C-cell lesions and others that support malignancy in borderline cases. The use of mutation-specific antibodies can distinguish papillary carcinomas harboring a BRAFV600E mutation from RAS-like neoplasms. Immunostains have been developed to further identify molecular alterations underlying tumor development, including some rearrangements. Altered expression of several biomarkers that are known to be epigenetically modified in thyroid cancer can be used to assist in predicting more aggressive behavior such as a propensity to develop locoregional lymphatic spread. Immunohistochemistry can assist in identifying lymphatic and vascular invasion. Biomarkers can be applied to determine dedifferentiation and to further classify poorly differentiated and anaplastic carcinomas. The rare tumors associated with genetic predisposition to endocrine neoplasia can also be identified using some immunohistochemical stains. The application of these ancillary tools allows more accurate diagnosis and better understanding of pathogenesis while improving prediction and prognosis for patients with thyroid neoplasms.

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References

  1. Asa SL, de Jesus AC, Kerr D et al. Thyroid. In: Mete O, Asa SL, editors. Endocrine Pathology. Cambridge: Cambridge University Press, 2016: 398–572.

    Google Scholar 

  2. Boerner SL, Asa SL. Biopsy Interpretation of the Thyroid. 2 ed. Philadelphia, PA: Wolters Kluwer, 2017.

  3. Mete O, Asa SL. Pitfalls in the diagnosis of follicular epithelial proliferations of the thyroid. Adv Anat Pathol 2012; 19(6):363–373.

    Article  PubMed  Google Scholar 

  4. Sequeira MJ, Morgan JM, Fuhrer D, Wheeler MH, Jasani B, Ludgate M. Thyroid transcription factor-2 gene expression in benign and malignant thyroid lesions. Thyroid 2001; 11(11):995–1001.

    Article  PubMed  CAS  Google Scholar 

  5. Ordonez NG. Thyroid transcription factor-1 is a marker of lung and thyroid carcinomas. Adv Anat Pathol 2000; 7(2):123–127.

    Article  PubMed  CAS  Google Scholar 

  6. Kimura S. Thyroid-specific transcription factors and their roles in thyroid cancer. J Thyroid Res 2011; 2011:710213, 1, 8.

  7. Katoh R, Kawaoi A, Miyagi E, Li X, Suzuki K, Nakamura Y, Kakudo K Thyroid transcription factor-1 in normal, hyperplastic, and neoplastic follicular thyroid cells examined by immunohistochemistry and nonradioactive in situ hybridization. Mod Pathol 2000; 13(5):570–576.

    Article  PubMed  CAS  Google Scholar 

  8. Katoh R, Miyagi E, Nakamura N et al. Expression of thyroid transcription factor-1 (TTF-1) in human C cells and medullary thyroid carcinomas. Hum Pathol 2000; 31(3):386–393.

    Article  PubMed  CAS  Google Scholar 

  9. Fernandez LP, Lopez-Marquez A, Santisteban P. Thyroid transcription factors in development, differentiation and disease. Nat Rev Endocrinol 2015; 11(1):29–42.

    Article  PubMed  CAS  Google Scholar 

  10. Agoff SN, Lamps LW, Philip AT, Amin MB, Schmidt RA, True LD, Folpe AL Thyroid transcription factor-1 is expressed in extrapulmonary small cell carcinomas but not in other extrapulmonary neuroendocrine tumors. Mod Pathol 2000; 13(3):238–242.

    Article  PubMed  CAS  Google Scholar 

  11. Ordonez NG. Value of thyroid transcription factor-1 immunostaining in tumor diagnosis: a review and update. Appl Immunohistochem Mol Morphol 2012; 20(5):429–444.

    Article  PubMed  CAS  Google Scholar 

  12. Ordonez NG. Thyroid transcription factor-1 is not expressed in squamous cell carcinomas of the lung: an immunohistochemical study with review of the literature. Appl Immunohistochem Mol Morphol 2012; 20(6):525–530.

    Article  PubMed  CAS  Google Scholar 

  13. Magno L, Kretz O, Bert B, Ersözlü S, Vogt J, Fink H, Kimura S, Vogt A, Monyer H, Nitsch R, Naumann T The integrity of cholinergic basal forebrain neurons depends on expression of Nkx2-1. Eur J Neurosci 2011; 34(11):1767–1782.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Rice SJ, Lai SC, Wood LW, Helsley KR, Runkle EA, Winslow MM, Mu D MicroRNA-33a mediates the regulation of high mobility group AT-hook 2 gene (HMGA2) by thyroid transcription factor 1 (TTF-1/NKX2-1). J Biol Chem 2013; 288(23):16348–16360.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Runkle EA, Rice SJ, Qi J, Masser D, Antonetti DA, Winslow MM, Mu D Occludin is a direct target of thyroid transcription factor-1 (TTF-1/NKX2-1). J Biol Chem 2012; 287(34):28790–28801.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. 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. Mod Pathol 2008; 21(2):192–200.

    Article  PubMed  CAS  Google Scholar 

  17. Castanet M, Leenhardt L, Leger J et al. Thyroid hemiagenesis is a rare variant of thyroid dysgenesis with a familial component but without Pax8 mutations in a cohort of 22 cases. Pediatr Res 2005; 57(6):908–913.

    Article  PubMed  CAS  Google Scholar 

  18. Di PT, Lucci V, de CT, Filippone MG, Zannini M. A role for PAX8 in the tumorigenic phenotype of ovarian cancer cells. BMC Cancer 2014; 14:292.

    Article  CAS  Google Scholar 

  19. Di PT, Filippone MG, Pierantoni GM, Fusco A, Soddu S, Zannini M. Pax8 has a critical role in epithelial cell survival and proliferation. Cell Death Dis 2013; 4:e729.

    Article  CAS  Google Scholar 

  20. Di PT, de CT, D'Ambrosio C, Del PD, Scaloni A, Zannini M. Poly(ADP-ribose) polymerase 1 binds to Pax8 and inhibits its transcriptional activity. J Mol Endocrinol 2008; 41(5):379–388.

    Article  CAS  Google Scholar 

  21. Bort R, Signore M, Tremblay K, Martinez Barbera JP, Zaret KS. Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development. Dev Biol 2006; 290(1):44–56.

    Article  PubMed  CAS  Google Scholar 

  22. Bort R, Martinez-Barbera JP, Beddington RS, Zaret KS. Hex homeobox gene-dependent tissue positioning is required for organogenesis of the ventral pancreas. Development 2004; 131(4):797–806.

    Article  PubMed  CAS  Google Scholar 

  23. Guo Y, Chan R, Ramsey H, Li W, Xie X, Shelley WC, Martinez-Barbera JP, Bort B, Zaret K, Yoder M, Hromas R The homeoprotein Hex is required for hemangioblast differentiation. Blood 2003; 102(7):2428–2435.

    Article  PubMed  CAS  Google Scholar 

  24. Kim JE, Ahn BC, Hwang MH, Jeon YH, Jeong SY, Lee SW, Lee J Combined RNA interference of hexokinase II and (131)I-sodium iodide symporter gene therapy for anaplastic thyroid carcinoma. J Nucl Med 2011; 52(11):1756–1763.

    Article  PubMed  CAS  Google Scholar 

  25. Martinez-Barbera JP, Beddington RS. Getting your head around Hex and Hesx1: forebrain formation in mouse. Int J Dev Biol 2001; 45(1):327–336.

    PubMed  CAS  Google Scholar 

  26. Martinez Barbera JP, Clements M, Thomas P, Rodriguez T, Meloy D, Kioussis D, Beddington RS The homeobox gene Hex is required in definitive endodermal tissues for normal forebrain, liver and thyroid formation. Development 2000; 127(11):2433–2445.

    PubMed  CAS  Google Scholar 

  27. Wu M, Szporn AH, Zhang D, Wasserman P, Gan L, Miller L, Burstein DE Cytology applications of p63 and TTF-1 immunostaining in differential diagnosis of lung cancers. Diagn Cytopathol 2005; 33(4):223–227.

    Article  PubMed  Google Scholar 

  28. Wu M, Wang B, Gil J, Sabo, E, Miller, L, Gan, L, Burstein, DE p63 and TTF-1 immunostaining. A useful marker panel for distinguishing small cell carcinoma of lung from poorly differentiated squamous cell carcinoma of lung. Am J Clin Pathol 2003; 119(5):696–702.

    PubMed  Google Scholar 

  29. Franc B, Caillou B, Carrier AM, Dutrieux-Berger N, Floquet J, Houcke M, Justrabo E, Lange F, Pages A, Rigaud C Immunohistochemistry in medullary thyroid carcinoma: prognosis and distinction between hereditary and sporadic tumors. Henry Ford Hosp Med J 1987; 35(2–3):139–142.

    PubMed  CAS  Google Scholar 

  30. Ziad EA, Ruchala M, Breborowicz J, Gembicki M, Sowinski J, Grzymislawski M. Immunoexpression of TTF-1 and Ki-67 in a coexistent anaplastic and follicular thyroid cancer with rare long-life surviving. Folia Histochem Cytobiol 2008; 46(4):461–464.

    Google Scholar 

  31. Shah AA, La FK, Miller C et al. Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia: a clinicopathologic and molecular analysis of a distinct entity. Mod Pathol 2017; 30(3):329–339.

    Article  PubMed  CAS  Google Scholar 

  32. Quiroga-Garza G, Lee JH, El-Naggar A et al. Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: more aggressive than previously reported. Hum Pathol 2015; 46(5):725–731.

    Article  PubMed  Google Scholar 

  33. Farhat NA, Faquin WC, Sadow PM. Primary mucoepidermoid carcinoma of the thyroid gland: a report of three cases and review of the literature. Endocr Pathol 2013; 24(4):229–233.

    Article  PubMed  Google Scholar 

  34. Ordonez NG. Utilization of thyroid transcription factor-1 immunostaining in the diagnosis of lung tumors. Methods Mol Med 2003; 75:355–368.

    PubMed  CAS  Google Scholar 

  35. Ordonez NG. Value of thyroid transcription factor-1 immunostaining in distinguishing small cell lung carcinomas from other small cell carcinomas. Am J Surg Pathol 2000; 24(9):1217–1223.

    Article  PubMed  CAS  Google Scholar 

  36. Rios Moreno MJ, Galera-Ruiz H, De MM, Lopez MI, Illanes M, Galera-Davidson H. Inmunohistochemical profile of solid cell nest of thyroid gland. Endocr Pathol 2011; 22(1):35–39.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Reis-Filho JS, Preto A, Soares P, Ricardo S, Cameselle-Teijeiro J, Sobrinho-Simoes M. p63 expression in solid cell nests of the thyroid: further evidence for a stem cell origin. Mod Pathol 2003; 16(1):43–48.

    Article  PubMed  Google Scholar 

  38. Manzoni M, Roversi G, Di BC et al. Solid cell nests of the thyroid gland: morphological, immunohistochemical and genetic features. Histopathology 2016; 68(6):866–874.

    Article  PubMed  Google Scholar 

  39. Asioli S, Erickson LA, Lloyd RV. Solid cell nests in Hashimoto’s thyroiditis sharing features with papillary thyroid microcarcinoma. Endocr Pathol 2009; 20(4):197–203.

    Article  PubMed  CAS  Google Scholar 

  40. Srbecka K, Michalova K, Curcikova R, Michal M, Dubova M, Svajdler M, Michal M, Daum O Spectrum of lesions derived from branchial arches occurring in the thyroid: from solid cell nests to tumors. Virchows Arch 2017; 471(3):393–400.

    Article  PubMed  CAS  Google Scholar 

  41. Gucer H, Mete O. Positivity for GATA3 and TTF-1 (SPT24), and Negativity for Monoclonal PAX8 Expand the Biomarker Profile of the Solid Cell Nests of the Thyroid Gland. Endocr Pathol 2018; 29(1):49–58.

    Article  PubMed  CAS  Google Scholar 

  42. Fischer S, Asa SL. Application of immunohistochemistry to thyroid neoplasms. Arch Pathol Lab Med 2008; 132(3):359–372.

    PubMed  Google Scholar 

  43. Liu H, Lin F. Application of immunohistochemistry in thyroid pathology. Arch Pathol Lab Med 2015; 139(1):67–82.

    Article  PubMed  Google Scholar 

  44. Sauter JL, Grogg KL, Vrana JA, Law ME, Halvorson JL, Henry MR. Young investigator challenge: Validation and optimization of immunohistochemistry protocols for use on cellient cell block specimens. Cancer Cytopathol 2016; 124(2):89–100.

    Article  PubMed  CAS  Google Scholar 

  45. Lacroix L, Mian C, Barrier T, Talbot M, Caillou B, Schlumberger M, Bidart J PAX8 and peroxisome proliferator-activated receptor gamma 1 gene expression status in benign and malignant thyroid tissues. Eur J Endocrinol 2004; 151(3):367–374.

    Article  PubMed  CAS  Google Scholar 

  46. Stelow EB, Yaziji H. Immunohistochemistry, carcinomas of unknown primary, and incidence rates. Semin Diagn Pathol 2018; 35(2):143–152.

    Article  PubMed  Google Scholar 

  47. Toriyama A, Mori T, Sekine S, Yoshida A, Hino O, Tsuta K. Utility of PAX8 mouse monoclonal antibody in the diagnosis of thyroid, thymic, pleural and lung tumours: a comparison with polyclonal PAX8 antibody. Histopathology 2014; 65(4):465–472.

    Article  PubMed  Google Scholar 

  48. Bishop JA, Sharma R, Westra WH. PAX8 immunostaining of anaplastic thyroid carcinoma: a reliable means of discerning thyroid origin for undifferentiated tumors of the head and neck. Hum Pathol 2011; 42(12):1873–1877.

    Article  PubMed  CAS  Google Scholar 

  49. Di JB, Arvan P. Thyroglobulin From Molecular and Cellular Biology to Clinical Endocrinology. Endocr Rev 2016; 37(1):2–36.

    Article  CAS  Google Scholar 

  50. Indrasena BS. Use of thyroglobulin as a tumour marker. World J Biol Chem 2017; 8(1):81–85.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Lin JD. Thyroglobulin and human thyroid cancer. Clin Chim Acta 2008; 388(1–2):15–21.

    Article  PubMed  CAS  Google Scholar 

  52. Lin JD, Huang MJ, Hsu BR et al. Significance of postoperative serum thyroglobulin levels in patients with papillary and follicular thyroid carcinomas. J Surg Oncol 2002; 80(1):45–51.

    Article  PubMed  CAS  Google Scholar 

  53. Wartofsky L. Management of low-risk well-differentiated thyroid cancer based only on thyroglobulin measurement after recombinant human thyrotropin. Thyroid 2002; 12(7):583–590.

    Article  PubMed  CAS  Google Scholar 

  54. Matias-Guiu X, De LR. Medullary thyroid carcinoma: a 25-year perspective. Endocr Pathol 2014; 25(1):21–29.

    Article  PubMed  CAS  Google Scholar 

  55. Sobrinho-Simoes M. Mixed medullary and follicular carcinoma of the thyroid. Histopathology 1993; 23(3):287–289.

    Article  PubMed  CAS  Google Scholar 

  56. Albores-Saavedra J, De La Mora TG, De La Torre-Rendon F, Gould E. Mixed medullary-papillary carcinoma of the thyroid: A previously unrecognized variant of thyroid carcinoma. Hum Pathol 1990; 21:1151–1155.

    Article  PubMed  CAS  Google Scholar 

  57. Mete O, Asa SL. Composite medullary and papillary thyroid carcinoma in a patient with MEN 2B. Case report and review of C-Cell lesions of the thyroid. Pathology Case Reviews 2009; 14(6):208–213.

    Article  Google Scholar 

  58. Apel RL, Alpert LC, Rizzo A, LiVolsi VA, Asa SL A metastasizing composite carcinoma of the thyroid with distinct medullary and papillary components. Arch Pathol Lab Med 1994; 118:1143–1147.

    PubMed  CAS  Google Scholar 

  59. Bournaud C, Charrie A, Nozieres C et al. Thyroglobulin measurement in fine-needle aspirates of lymph nodes in patients with differentiated thyroid cancer: a simple definition of the threshold value, with emphasis on potential pitfalls of the method. Clin Chem Lab Med 2010; 48(8):1171–1177.

    Article  PubMed  CAS  Google Scholar 

  60. Salmaslioglu A, Erbil Y, Citlak G et al. Diagnostic value of thyroglobulin measurement in fine-needle aspiration biopsy for detecting metastatic lymph nodes in patients with papillary thyroid carcinoma. Langenbecks Arch Surg 2011; 396(1):77–81.

    Article  PubMed  Google Scholar 

  61. Savin S, Cvejic D, Isic T, Petrovic I, Paunovic I, Tatic S, Havelka M Thyroid peroxidase immunohistochemistry in differential diagnosis of thyroid tumors. Endocr Pathol 2006; 17(1):53–60.

    Article  PubMed  CAS  Google Scholar 

  62. Williams ED. A review of 17 cases of carcinoma of the thyroid and phaeochromocytoma. J Clin Pathol 1965; 18:288–292.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Williams ED. Histiogenesis of medullary carcinoma of the thyroid. J Clin Pathol 1966; 19:114–118.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Bussolati G, Pearse AG. Immunofluorescent localization of calcitonin in the ‘C’ cells of pig and dog thyroid. J Endocrinol 1967; 37(2):205–209.

    Article  PubMed  CAS  Google Scholar 

  65. Davey RA, Findlay DM. Calcitonin: physiology or fantasy? J Bone Miner Res 2013; 28(5):973–979.

    Article  PubMed  CAS  Google Scholar 

  66. Findlay DM, Sexton PM. Growth Factors 2004; 22(4):217–224, Calcitonin.

    Article  PubMed  CAS  Google Scholar 

  67. DeLellis RA, Wolfe HJ. The pathobiology of the human calcitonin (C)-cell: a review. Pathol Annu 1981; 16:25–52.

    CAS  Google Scholar 

  68. Wells SA, Jr., Asa SL, Dralle H et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 2015; 25(6):567–610.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Dora JM, Canalli MH, Capp C, Punales MK, Vieira JG, Maia AL. Normal perioperative serum calcitonin levels in patients with advanced medullary thyroid carcinoma: case report and review of the literature. Thyroid 2008; 18(8):895–899.

    Article  PubMed  CAS  Google Scholar 

  70. Chernyavsky VS, Farghani S, Davidov T, Ma L, Barnard N, Amorosa LF, Trooskin SZ Calcitonin-negative neuroendocrine tumor of the thyroid: a distinct clinical entity. Thyroid 2011; 21(2):193–196.

    Article  PubMed  CAS  Google Scholar 

  71. Brutsaert EF, Gersten AJ, Tassler AB, Surks MI. Medullary thyroid cancer with undetectable serum calcitonin. J Clin Endocrinol Metab 2015; 100(2):337–341.

    Article  PubMed  CAS  Google Scholar 

  72. Laure GA, Al GA, Auperin A et al. Progression of medullary thyroid carcinoma: assessment with calcitonin and carcinoembryonic antigen doubling times. Eur J Endocrinol 2008; 158(2):239–246.

    Article  CAS  Google Scholar 

  73. Girelli ME, Dotto S, Nacamulli D, Piccolo M, de Vido D, Russo T, Bernante P, Pelizzo MR, Busnardo B Prognostic value of early postoperative calcitonin level in medullary thyroid carcinoma. Tumori 1994; 80(2):113–117.

    Article  PubMed  CAS  Google Scholar 

  74. Steenbergh PH, Hoppener JW, Zandberg J, Van de Ven WJ, Jansz HS, Lips CJ. Calcitonin gene related peptide coding sequence is conserved in the human genome and is expressed in medullary thyroid carcinoma. J Clin Endocrinol Metab 1984; 59(2):358–360.

    Article  PubMed  CAS  Google Scholar 

  75. Höppener JWM, Steenbergh PH, Moonen PJJ, Wagenaar SjSc, Jansz HS, Lips CJM. Detection of mRNA encoding calcitonin, calcitonin gene related peptide and proopiomelanocortin in human tumors. Mol Cell Endocrinol 1986; 47:125–130.

    Article  PubMed  Google Scholar 

  76. Schifter S. Expression of the calcitonin gene family in medullary thyroid carcinoma. Peptides 1997; 18(2):307–317.

    Article  PubMed  CAS  Google Scholar 

  77. Lee SM, Policarpio-Nicolas ML. Arch Pathol Lab Med 2015; 139(8):1062–1067, Thyroid Paraganglioma.

    Article  PubMed  CAS  Google Scholar 

  78. von Dobschuetz E, Leijon H, Schalin-Jantti C, Schiavi F, Brauckhoff M, Peczkowska M, Spiazzi G, Dematte S, Cecchini ME, Sartorato P, Krajewska J, Hasse-Lazar K, Roszkowska-Purska K, Taschin E, Malinoc A, Akslen LA, Arola J, Lange D, Fassina A, Pennelli G, Barbareschi M, Luettges J, Prejbisz A, Januszewicz A, Strate T, Bausch B, Castinetti F, Jarzab B, Opocher G, Eng C, Neumann HPH A registry-based study of thyroid paraganglioma: histological and genetic characteristics. Endocr Relat Cancer 2015; 22(2):191–204.

    Article  CAS  Google Scholar 

  79. Castelblanco E, Gallel P, Ros S, Gatius S, Valls J, de-Cubas AA, Maliszewska A, Yebra-Pimentel MT, Menarguez J, Gamallo C, Opocher G, Robledo M, Matias-Guiu X Thyroid paraganglioma. Report of 3 cases and description of an immunohistochemical profile useful in the differential diagnosis with medullary thyroid carcinoma, based on complementary DNA array results. Hum Pathol 2012; 43(7):1103–1112.

    Article  PubMed  CAS  Google Scholar 

  80. Miettinen M, McCue PA, Sarlomo-Rikala M et al. GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors. Am J Surg Pathol 2014; 38(1):13–22.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Liu H, Shi J, Wilkerson ML, Lin F. Immunohistochemical evaluation of GATA3 expression in tumors and normal tissues: a useful immunomarker for breast and urothelial carcinomas. Am J Clin Pathol 2012; 138(1):57–64.

    Article  PubMed  Google Scholar 

  82. Ordonez NG. Value of GATA3 immunostaining in tumor diagnosis: a review. Adv Anat Pathol 2013; 20(5):352–360.

    Article  PubMed  CAS  Google Scholar 

  83. Mete O, Tischler AS, de KR et al. Protocol for the examination of specimens from patients with pheochromocytomas and extra-adrenal paragangliomas. Arch Pathol Lab Med 2014; 138(2):182–188.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Osinga TE, Korpershoek E, de Krijger RR, Kerstens MN, Dullaart RPF, Kema IP, van der Laan BFAM, van der Horst-Schrivers ANA, Links TP Catecholamine-Synthesizing Enzymes Are Expressed in Parasympathetic Head and Neck Paraganglioma Tissue. Neuroendocrinology 2015; 101(4):289–295.

    Article  PubMed  CAS  Google Scholar 

  85. Mete O, Essa A, Bramdev A, Govender N, Chetty R. MEN2 Syndrome-Related Medullary Thyroid Carcinoma with Focal Tyrosine Hydroxylase Expression: Does It Represent a Hybrid Cellular Phenotype or Functional State of Tumor Cells? Endocr Pathol 2017; 28(4):362–366.

    Article  PubMed  CAS  Google Scholar 

  86. Duan K, Mete O. Algorithmic approach to neuroendocrine tumors in targeted biopsies: Practical applications of immunohistochemical markers. Cancer Cytopathol 2016; 124(12):871–884.

    Article  PubMed  Google Scholar 

  87. Wilhelm SM, Wang TS, Ruan DT, Lee JA, Asa SL, Duh QY, Doherty GM, Herrera MF, Pasieka JL, Perrier ND, Silverberg SJ, Solórzano CC, Sturgeon C, Tublin ME, Udelsman R, Carty SE The American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism. JAMA Surg 2016; 151(10):959–968.

    Article  PubMed  Google Scholar 

  88. Duan K, Gomez HK, Mete O. Clinicopathological correlates of hyperparathyroidism. J Clin Pathol 2015; 68(10):771–787.

    Article  PubMed  CAS  Google Scholar 

  89. Takada N, Hirokawa M, Suzuki A, Higuchi M, Kuma S, Miyauchi A. Diagnostic value of GATA-3 in cytological identification of parathyroid tissues. Endocr J 2016; 63(7):621–626.

    Article  PubMed  CAS  Google Scholar 

  90. Ordonez NG. Value of GATA3 immunostaining in the diagnosis of parathyroid tumors. Appl Immunohistochem Mol Morphol 2014; 22(10):756–761.

    Article  PubMed  CAS  Google Scholar 

  91. LiVolsi VA. Branchial and thymic remnants in the thyroid and cervical region: An explanation for unusual tumors and microscopic curiosities. Endocr Pathol 1993; 4:115–119.

    Article  Google Scholar 

  92. Nonaka D. Study of parathyroid transcription factor Gcm2 expression in parathyroid lesions. Am J Surg Pathol 2011; 35(1):145–151.

    Article  PubMed  Google Scholar 

  93. Harach HR, Vujanic GM, Jasani B. Ultimobranchial body nests in human fetal thyroid: An autopsy, histological, and immunohistochemical study in relation to solid cell nests and mucoepidermoid carcinoma of the thyroid. J Pathol 1993; 169:465–469.

    Article  PubMed  CAS  Google Scholar 

  94. Chan JK, Rosai J. Tumors of the neck showing thymic or related branchial pouch differentiation: a unifying concept. Hum Pathol 1991; 22(4):349–367.

    Article  PubMed  CAS  Google Scholar 

  95. Weissferdt A, Moran CA. Ectopic primary intrathyroidal thymoma: a clinicopathological and immunohistochemical analysis of 3 cases. Hum Pathol 2016; 49:71–76.

    Article  PubMed  CAS  Google Scholar 

  96. Weissferdt A, Kalhor N, Bishop JA, Jang SJ, Ro J, Petersson F, Wu B, Langman G, Bancroft H, Bi Y, Meng Y, Medeiros F, Brunnstrom H, Spagnolo D, Chai SM, Laycock A, Wakely Jr PE, Elmberger G, Soares FA, Campos AH, Gumurdulu D, Alvarado-Cabrero I, Coppola D, Correa AM, Rice D, Mehran RJ, Sepesi B, Walsh G, Kaiser L, Moran CA Thymoma: a clinicopathological correlation of 1470 cases. Hum Pathol 2018; 73:7–15.

    Article  PubMed  Google Scholar 

  97. Taweevisit M, Sampatanukul P, Thorner PS. Ectopic thymoma can mimic benign and malignant thyroid lesions on fine needle aspiration cytology: a case report and literature review. Acta Cytol 2013; 57(2):213–220.

    Article  PubMed  Google Scholar 

  98. Kakudo K, Bai Y, Ozaki T, Homma K, Ito Y, Miyauchi A. Intrathyroid epithelial thymoma (ITET) and carcinoma showing thymus-like differentiation (CASTLE): CD5-positive neoplasms mimicking squamous cell carcinoma of the thyroid. Histol Histopathol 2013; 28(5):543–556.

    PubMed  Google Scholar 

  99. Asa SL, Giordano TJ, LiVolsi VA. Implications of the TCGA genomic characterization of papillary thyroid carcinoma for thyroid pathology: does follicular variant papillary thyroid carcinoma exist? Thyroid 2015; 25(1):1–2.

    Article  PubMed  Google Scholar 

  100. Apel RL, Ezzat S, Bapat B, Pan N, LiVolsi VA, Asa SL. Clonality of thyroid nodules in sporadic goiter. Diag Mol Pathol 1995; 4:113–121.

    Article  CAS  Google Scholar 

  101. Lloyd RV, Erickson LA, Casey MB, Lam KY, Lohse CM, Asa SL, Chan JKC, DeLellis RA, Harach HR, Kakudo K, LiVolsi VA, Rosai J, Sebo TJ, Sobrinho-Simoes M, Wenig BM, Lae ME Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma. Am J Surg Pathol 2004; 28(10):1336–1340.

    Article  PubMed  Google Scholar 

  102. Elsheikh TM, Asa SL, Chan JK et al. Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions with borderline nuclear features of papillary carcinoma. Am J Clin Pathol 2008; 130(5):736–744.

    Article  PubMed  Google Scholar 

  103. Hirokawa M, Carney JA, Goellner JR, DeLellis RA, Heffess CS, Katoh R, Tsujimoto M, Kakudo K Observer variation of encapsulated follicular lesions of the thyroid gland. Am J Surg Pathol 2002; 26(11):1508–1514.

    Article  PubMed  Google Scholar 

  104. Papotti M, Manazza AD, Chiarle R, Bussolati G. Confocal microscope analysis and tridimensional reconstruction of papillary thyroid carcinoma nuclei. Virchows Arch 2004; 444(4):350–355.

    Article  PubMed  Google Scholar 

  105. Eldar S, Sabo E, Cohen A, Misselevich I, Abrahamson J, Cohen O, Kelner J, Boss JH The value of histomorphometric nuclear parameters in the diagnosis of well differentiated follicular carcinomas and follicular adenomas of the thyroid gland. Histopathology 1999; 34(5):453–461.

    Article  PubMed  CAS  Google Scholar 

  106. Asioli S, Maletta F, Pacchioni D, Lupo R, Bussolati G. Cytological detection of papillary thyroid carcinomas by nuclear membrane decoration with emerin staining. Virchows Arch 2010; 457(1):43–51.

    Article  PubMed  CAS  Google Scholar 

  107. Asioli S, Bussolati G. Emerin immunohistochemistry reveals diagnostic features of nuclear membrane arrangement in thyroid lesions. Histopathology 2009; 54(5):571–579.

    Article  PubMed  Google Scholar 

  108. Nikiforov YE, Seethala RR, Tallini G, Baloch ZW, Basolo F, Thompson LDR, Barletta JA, Wenig BM, al Ghuzlan A, Kakudo K, Giordano TJ, Alves VA, Khanafshar E, Asa SL, el-Naggar AK, Gooding WE, Hodak SP, Lloyd RV, Maytal G, Mete O, Nikiforova MN, Nosé V, Papotti M, Poller DN, Sadow PM, Tischler AS, Tuttle RM, Wall KB, LiVolsi VA, Randolph GW, Ghossein RA Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors. JAMA Oncol 2016; 2(8):1023–1029.

    Article  PubMed  PubMed Central  Google Scholar 

  109. The Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell 2014; 159(3):676–690.

    Article  CAS  Google Scholar 

  110. Seethala RR, Baloch ZW, Barletta JA, Khanafshar E, Mete O, Sadow PM, LiVolsi VA, Nikiforov YE, Tallini G, Thompson LDR Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a review for pathologists. Mod Pathol 2018; 31(1):39–55.

    Article  PubMed  CAS  Google Scholar 

  111. Lloyd RV, Asa SL, LiVolsi VA et al. The evolving diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Hum Pathol 2018, 74, 1, 4.

    Article  PubMed  Google Scholar 

  112. Reagh J, Bullock M, Andrici J, Turchini J, Sioson L, Clarkson A, Watson N, Sheen A, Lim G, Delbridge L, Sidhu S, Sywak M, Aniss A, Shepherd P, Ng D, Oei P, Field M, Learoyd D, Robinson BG, Clifton-Bligh RJ, Gill AJ NRASQ61R Mutation-specific Immunohistochemistry Also Identifies the HRASQ61R Mutation in Medullary Thyroid Cancer and May Have a Role in Triaging Genetic Testing for MEN2. Am J Surg Pathol 2017; 41(1):75–81.

    Article  PubMed  Google Scholar 

  113. Cheung CC, Carydis B, Ezzat S, Bedard YC, Asa SL. Analysis of ret/PTC gene rearrangements refines the fine needle aspiration diagnosis of thyroid cancer. J Clin Endocrinol Metab 2001; 86(5):2187–2190.

    Article  PubMed  CAS  Google Scholar 

  114. Serra S, Asa SL. Controversies in Thyroid Pathology: The Diagnosis of Follicular Neoplasms. Endocr Pathol 2008, 19, 156, 165.

    Article  PubMed  Google Scholar 

  115. Dunderovic D, Lipkovski JM, Boricic I et al. Defining the value of CD56, CK19, Galectin 3 and HBME-1 in diagnosis of follicular cell derived lesions of thyroid with systematic review of literature. Diagn Pathol 2015; 10:196.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Prasad ML, Pellegata NS, Huang Y, Nagaraja HN, Chapelle AL, Kloos RT. Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Mod Pathol 2005; 18(1):48–57.

    Article  PubMed  CAS  Google Scholar 

  117. Papotti M, Rodriguez J, De Pompa R, Bartolazzi A, Rosai J. Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential. Mod Pathol 2005; 18(4):541–546.

    Article  PubMed  CAS  Google Scholar 

  118. Prasad ML, Pellegata NS, Huang Y, Nagaraja HN, Chapelle AA, Kloos RT. Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Mod Pathol 2004.

  119. Volante M, Bozzalla-Cassione F, DePompa R, Saggiorato E, Bartolazzi A, Orlandi F, Papotti M Galectin-3 and HBME-1 expression in oncocytic cell tumors of the thyroid. Virchows Arch 2004; 445(2):183–188.

    Article  PubMed  CAS  Google Scholar 

  120. Casey MB, Lohse CM, Lloyd RV. Distinction between papillary thyroid hyperplasia and papillary thyroid carcinoma by immunohistochemical staining for cytokeratin 19, galectin-3, and HBME-1. Endocr Pathol 2003; 14(1):55–60.

    Article  PubMed  Google Scholar 

  121. Sack MJ, Astengo-Osuna C, Lin BT, Battifora H, LiVolsi VA. HBME-1 immunostaining in thyroid fine-needle aspirations: a useful marker in the diagnosis of carcinoma. Mod Pathol 1997; 10:668–674.

    PubMed  CAS  Google Scholar 

  122. van Hoeven KH, Kovatich AJ, Miettinen M. Immunocytochemical evaluation of HBME-1, CA 19-9, and CD-15 (Leu-M1) in fine-needle aspirates of thyroid nodules. Diagn Cytopathol 1997; 18:93–97.

    Article  Google Scholar 

  123. Miettinen M, Karkkainen P. Differential reactivity of HBME-1 and CD15 antibodies in benign and malignant thyroid tumours. Preferential reactivity with malignant tumours. Virchows Arch 1996; 429:213–219.

    PubMed  CAS  Google Scholar 

  124. Cheung CC, Ezzat S, Freeman JL, Rosen IB, Asa SL. Immunohistochemical diagnosis of papillary thyroid carcinoma. Mod Pathol 2001; 14(4):338–342.

    Article  PubMed  CAS  Google Scholar 

  125. Cheng S, Serra S, Mercado M, Ezzat S, Asa SL. A high-throughput proteomic approach provides distinct signatures for thyroid cancer behavior. Clin Cancer Res 2011; 17(8):2385–2394.

    Article  PubMed  CAS  Google Scholar 

  126. Gucer H, Bagci P, Bedir R, Sehitoglu I, Mete O. The Value of HBME-1 and Claudin-1 Expression Profile in the Distinction of BRAF-Like and RAS-Like Phenotypes in Papillary Thyroid Carcinoma. Endocr Pathol 2016; 27(3):224–232.

    Article  PubMed  CAS  Google Scholar 

  127. Jin L, Riss D, Ruebel K, Kajita S, Scheithauer BW, Horvath E, Kovacs K, Lloyd RV Galectin-3 Expression in Functioning and Silent ACTH-Producing Adenomas. Endocr Pathol 2005; 16(2):107–114.

    Article  PubMed  CAS  Google Scholar 

  128. Bergero N, De Pompa R, Sacerdote C et al. Galectin-3 expression in parathyroid carcinoma: immunohistochemical study of 26 cases. Hum Pathol 2005; 36(8):908–914.

    Article  PubMed  CAS  Google Scholar 

  129. Cvejic DS, Savin SB, Petrovic IM, Paunovic IR, Tatic SB, Havelka MJ. Galectin-3 expression in papillary thyroid carcinoma: relation to histomorphologic growth pattern, lymph node metastasis, extrathyroid invasion, and tumor size. Head Neck 2005; 27(12):1049–1055.

    Article  PubMed  Google Scholar 

  130. Mehrotra P, Okpokam A, Bouhaidar R, Johnson SJ, Wilson JA, Davies BR, Lennard TWJ Galectin-3 does not reliably distinguish benign from malignant thyroid neoplasms. Histopathology 2004; 45(5):493–500.

    Article  PubMed  CAS  Google Scholar 

  131. Kawachi K, Matsushita Y, Yonezawa S, Nakano S, Shirao K, Natsugoe S, Sueyoshi K, Aikou T, Sato E Galectin-3 expression in various thyroid neoplasms and its possible role in metastasis formation. Hum Pathol 2000; 31(4):428–433.

    Article  PubMed  CAS  Google Scholar 

  132. Cvejic D, Savin S, Golubovic S, Paunovic I, Tatic S, Havelka M. Galectin-3 and carcinoembryonic antigen expression in medullary thyroid carcinoma: possible relation to tumour progression. Histopathology 2000; 37(6):530–535.

    Article  PubMed  CAS  Google Scholar 

  133. Inohara H, Honjo Y, Yoishii T et al. Expression of galectin-3 in fine-needle aspirates as a diagnostic marker differentiating benign from malignant thyroid neoplasms. Cancer 1999; 85:2475–2484.

    Article  PubMed  CAS  Google Scholar 

  134. Orlandi F, Saggiorato E, Pivano G, Puligheddu B, Termine A, Cappia S, de Giuli P, Angeli A Galectin-3 is a presurgical marker of human thyroid carcinoma. Cancer Res 1998; 58:3015–3020.

    PubMed  CAS  Google Scholar 

  135. Cvejic D, Savin S, Paunovic I, Tatic S, Havelka M, Sindinovic J. Immuhohistochemical localization of galectin-3 in malignant and benign human thyroid tissue. Anticancer Res 1998; 18:2637–2642.

    PubMed  CAS  Google Scholar 

  136. Fernandez PL, Merino MJ, Gomez M et al. Galectin-3 and laminin expression in neoplastic and non-neoplastic thyroid tissue. J Pathol 1997; 181:80–86.

    Article  PubMed  CAS  Google Scholar 

  137. Xu XC, El Naggar AK, Lotan R. Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications. Am J Pathol 1995; 147(3):815–822.

    PubMed  PubMed Central  CAS  Google Scholar 

  138. Sahoo S, Hoda SA, Rosai J, DeLellis RA. Cytokeratin 19 immunoreactivity in the diagnosis of papillary thyroid carcinoma: a note of caution. Am J Clin Pathol 2001; 116(5):696–702.

    Article  PubMed  CAS  Google Scholar 

  139. Kragsterman B, Grimelius L, Walin G, Werga P, Johansson H. Cytokeratin 19 expression in papillary thyroid carcinoma. Appl Immunohistochem Mol Morphol 1999; 7:181–185.

    CAS  Google Scholar 

  140. Raphael SJ, Apel RL, Asa SL. Detection of high-molecular-weight cytokeratins in neoplastic and non-neoplastic thyroid tumors using microwave antigen retrieval. Mod Pathol 1995; 8:870–872.

    PubMed  CAS  Google Scholar 

  141. Henzen-Logmans SC, Mullink H, Ramaekers RCS, Tadema T, Meijer CJLM. Expression of cytokeratins and vimentin in epithelial cells of normal and pathologic thyroid tissue. Virchows Archives [Pathol Anat] 410, 347–354. 1987.

    Article  CAS  Google Scholar 

  142. Asa SL, Cheung CC. The mind’s eye. Am J Clin Pathol 2001; 116(5):635–636.

    Article  PubMed  CAS  Google Scholar 

  143. Ghossein RA, Katabi N, Fagin JA. Immunohistochemical detection of mutated BRAF V600E supports the clonal origin of BRAF-induced thyroid cancers along the spectrum of disease progression. J Clin Endocrinol Metab 2013; 98(8):E1414-E1421.

    Article  PubMed  CAS  Google Scholar 

  144. Crescenzi A, Guidobaldi L, Nasrollah N, Taccogna S, Cicciarella Modica DD, Turrini L, Nigri G, Romanelli F, Valabrega S, Giovanella L, Onetti Muda A, Trimboli P Immunohistochemistry for BRAF(V600E) antibody VE1 performed in core needle biopsy samples identifies mutated papillary thyroid cancers. Horm Metab Res 2014; 46(5):370–374.

    Article  PubMed  CAS  Google Scholar 

  145. Virk RK, Theoharis CG, Prasad A, Chhieng D, Prasad ML. Morphology predicts BRAF (V(6)(0)(0)E) mutation in papillary thyroid carcinoma: an interobserver reproducibility study. Virchows Arch 2014; 464(4):435–442.

    Article  PubMed  CAS  Google Scholar 

  146. Kondo T, Ezzat S, Asa SL. Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer 2006; 6(4):292–306.

    Article  PubMed  CAS  Google Scholar 

  147. Chou A, Fraser S, Toon CW, Clarkson A, Sioson L, Farzin M, Cussigh C, Aniss A, O’Neill C, Watson N, Clifton-Bligh RJ, Learoyd DL, Robinson BG, Selinger CI, Delbridge LW, Sidhu SB, O’Toole SA, Sywak M, Gill AJ A detailed clinicopathologic study of ALK-translocated papillary thyroid carcinoma. Am J Surg Pathol 2015; 39(5):652–659.

    Article  PubMed  PubMed Central  Google Scholar 

  148. Ito Y, Miyauchi A, Ishikawa H, Hirokawa M, Kudo T, Tomoda C, Miya A Our experience of treatment of cribriform morular variant of papillary thyroid carcinoma; difference in clinicopathological features of FAP-associated and sporadic patients. Endocr J 2011; 58(8):685–689.

    Article  PubMed  Google Scholar 

  149. Xu B, Yoshimoto K, Miyauchi A, Kuma S, Mizusawa N, Hirokawa M, Sano T Cribriform-morular variant of papillary thyroid carcinoma: a pathological and molecular genetic study with evidence of frequent somatic mutations in exon 3 of the beta-catenin gene. J Pathol 2003; 199(1):58–67.

    Article  PubMed  CAS  Google Scholar 

  150. Volante M, Collini P, Nikiforov YE, Sakamoto A, Kakudo K, Katoh R, Lloyd RV, LiVolsi VA, Papotti M, Sobrinho-Simoes M, Bussolati G, Rosai J Poorly differentiated thyroid carcinoma: the Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am J Surg Pathol 2007; 31(8):1256–1264.

    Article  PubMed  Google Scholar 

  151. Prasad ML, Pellegata NS, Kloos RT, Barbacioru C, Huang Y, de la CA. CITED1 protein expression suggests Papillary Thyroid Carcinoma in high throughput tissue microarray-based study. Thyroid 2004; 14(3):169–175.

    Article  PubMed  CAS  Google Scholar 

  152. Nasir A, Catalano E, Calafati S, Cantor A, Kaiser HE, Coppola D. Role of p53, CD44V6 and CD57 in differentiating between benign and malignant follicular neoplasms of the thyroid. In Vivo 2004; 18(2):189–195.

    PubMed  CAS  Google Scholar 

  153. Khoo ML, Ezzat S, Freeman JL, Asa SL. Cyclin D1 protein expression predicts metastatic behavior in thyroid papillary microcarcinomas but is not associated with gene amplification. J Clin Endocrinol Metab 2002; 87(4):1810–1813.

    Article  PubMed  CAS  Google Scholar 

  154. Khoo ML, Beasley NJ, Ezzat S, Freeman JL, Asa SL. Overexpression of cyclin D1 and underexpression of p27 predict lymph node metastases in papillary thyroid carcinoma. J Clin Endocrinol Metab 2002; 87(4):1814–1818.

    Article  PubMed  CAS  Google Scholar 

  155. Khoo ML, Freeman JL, Witterick IJ et al. Underexpression of p27/Kip in thyroid papillary microcarcinomas with gross metastatic disease. Arch Otolaryngol Head Neck Surg 2002; 128(3):253–257.

    Article  PubMed  Google Scholar 

  156. Asa SL, Ezzat S. The epigenetic landscape of differentiated thyroid cancer. Mol Cell Endocrinol 2017.

  157. Liu W, Asa SL, Fantus IG, Walfish PG, Ezzat S. Vitamin D arrests thyroid carcinoma cell growth and induces p27 dephosphorylation and accumulation through PTEN/akt-dependent and -independent pathways. Am J Pathol 2002; 160(2):511–519.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. Dackiw AP, Ezzat S, Huang P, Liu W, Asa SL. Vitamin D3 Administration Induces Nuclear p27 Accumulation, Restores Differentiation, and Reduces Tumor Burden in a Mouse Model of Metastatic Follicular Thyroid Cancer. Endocrinology 2004; 145(12):5840–5846.

    Article  PubMed  CAS  Google Scholar 

  159. Sponziello M, Rosignolo F, Celano M, Maggisano V, Pecce V, de Rose RF, Lombardo GE, Durante C, Filetti S, Damante G, Russo D, Bulotta S Fibronectin-1 expression is increased in aggressive thyroid cancer and favors the migration and invasion of cancer cells. Mol Cell Endocrinol 2016; 431:123–132.

    Article  PubMed  CAS  Google Scholar 

  160. Liu W, Cheng S, Asa SL, Ezzat S. The melanoma-associated antigen A3 mediates fibronectin-controlled cancer progression and metastasis. Cancer Res 2008; 68(19):8104–8112.

    Article  PubMed  CAS  Google Scholar 

  161. Liu W, Asa SL, Ezzat S. 1{alpha},25-Dihydroxyvitamin D3 Targets PTEN-Dependent Fibronectin Expression to Restore Thyroid Cancer Cell Adhesiveness. Mol Endocrinol 2005; 19(9):2349–2357.

    Article  PubMed  CAS  Google Scholar 

  162. Cheng S, Liu W, Mercado M, Ezzat S, Asa SL. Expression of the melanoma-associated antigen is associated with progression of human thyroid cancer. Endocr Relat Cancer 2009; 16(2):455–466.

    Article  PubMed  CAS  Google Scholar 

  163. Liu W, Wei W, Winer D, Bamberger AM, Bamberger C, Wagener C, Ezzat S, Asa SL CEACAM1 impedes thyroid cancer growth but promotes invasiveness: a putative mechanism for early metastases. Oncogene 2007; 26(19):2747–2758.

    Article  PubMed  CAS  Google Scholar 

  164. Liu W, Guo M, Ezzat S, Asa SL. Vitamin D inhibits CEACAM1 to promote insulin/IGF-I receptor signaling without compromising anti-proliferative action. Lab Invest 2011; 91(1):147–156.

    Article  PubMed  CAS  Google Scholar 

  165. Guarino V, Faviana P, Salvatore G, Castellone MD, Cirafici AM, de Falco V, Celetti A, Giannini R, Basolo F, Melillo RM, Santoro M Osteopontin is overexpressed in human papillary thyroid carcinomas and enhances thyroid carcinoma cell invasiveness. J Clin Endocrinol Metab 2005; 90(9):5270–5278.

    Article  PubMed  CAS  Google Scholar 

  166. Briese J, Ezzat S, Liu W et al. Osteopontin expression in thyroid carcinoma. Anticancer Res 2010; 30(7):111–122.

    Google Scholar 

  167. Nellore A, Paziana K, Ma C, Tsygankova OM, Wang Y, Puttaswamy K, Iqbal AU, Franks SR, Lv Y, Troxel AB, Feldman MD, Meinkoth JL, Brose MS Loss of Rap1GAP in papillary thyroid cancer. J Clin Endocrinol Metab 2009; 94(3):1026–1032.

    Article  PubMed  CAS  Google Scholar 

  168. Mete O, Asa SL. Pathological definition and clinical significance of vascular invasion in thyroid carcinomas of follicular epithelial derivation. Mod Pathol 2011; 24(12):1545–1552.

    Article  PubMed  Google Scholar 

  169. Basolo F, Caligo MA, Pinchera A, Fedeli F, Baldanzi A, Miccoli P, Iacconi P, Fontanini G, Pacini F Cyclin D1 overexpression in thyroid carcinomas: relation with clinico-pathological parameters, retinoblastoma gene product, and Ki67 labeling index. Thyroid 2000; 10(9):741–746.

    Article  PubMed  CAS  Google Scholar 

  170. Tallini G, Garcia-Rostan G, Herrero A, Zelterman D, Viale G, Bosari S, Carcangiu ML Downregulation of p27KIP1 and Ki67/Mib1 labeling index support the classification of thyroid carcinoma into prognostically relevant categories. Am J Surg Pathol 1999; 23(6):678–685.

    Article  PubMed  CAS  Google Scholar 

  171. Kendall CH, Sanderson PR, Cope J, Talbot IC. Follicular thyroid tumours: a study of laminin and type IV collagen in basement membrane and endothelium. J Clin Pathol 1985; 38:1100–1105.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  172. Laury AR, Bongiovanni M, Tille JC, Kozakewich H, Nose V. Thyroid pathology in PTEN-hamartoma tumor syndrome: characteristic findings of a distinct entity. Thyroid 2011; 21(2):135–144.

    Article  PubMed  Google Scholar 

  173. Ni Y, Zbuk KM, Sadler T, Patocs A, Lobo G, Edelman E, Platzer P, Orloff MS, Waite KA, Eng C Germline mutations and variants in the succinate dehydrogenase genes in Cowden and Cowden-like syndromes. Am J Hum Genet 2008; 83(2):261–268.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  174. Cameselle-Teijeiro J, Chan JK. Cribiform-morular variant of papillary carcinoma: a distinct variant representing the sporadic counterpart of familial adenomatous polyposis-associated with thyroid carcinoma. Mod Pathol 1999; 12:400–411.

    PubMed  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank Dr. Anthony Gill for providing Fig. 7b and c.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Zubair Baloch

  2. Department of Pathology, Laboratory Medicine Program, University Health Network, Toronto, ON, Canada

    Ozgur Mete & Sylvia L. Asa

  3. Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada

    Ozgur Mete & Sylvia L. Asa

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  1. Zubair Baloch
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OM, ZB, and SLA were responsible for the concept and design of the study; ZB, SLA, and OM for the writing of the manuscript; OM, SLA, and ZB for the critical reviews; and OM for the photomicrographs (except Fig. 7b and c).

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Correspondence to Ozgur Mete.

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Baloch, Z., Mete, O. & Asa, S.L. Immunohistochemical Biomarkers in Thyroid Pathology. Endocr Pathol 29, 91–112 (2018). https://doi.org/10.1007/s12022-018-9532-9

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