Immunohistochemistry in Diagnostic Parathyroid Pathology

Article

Abstract

Pathologists are usually readily able to diagnose parathyroid tissues and diseases, particularly when they have knowledge of the clinical information, laboratory findings, and radiographic imaging studies. However, the identification of parathyroid tissue or lesions can be difficult in small biopsies, ectopic locations, supranumerary glands, and in some oxyphil/oncocytic lesions. Widely available immunohistochemical studies such as chromogranin-A, synaptophysin, keratin, parathyroid hormone, thyroglobulin, and thyroid transcription factor-1 can help in difficult cases. One of the most difficult diagnostic aspects faced by the pathologist in evaluating parathyroid is distinguishing between parathyroid adenoma, particularly atypical adenoma, and parathyroid carcinoma. Many markers have and continue to be evaluated for diagnostic utility, and are even beginning to be studied for prognostic utility. Single immunohistochemical markers such as parafibromin and Ki-67 are among the most studied and most utilized, but many additional markers have and continue to be evaluated such as galectin-3, PGP9.5, Rb, bcl2, p27, hTERT, mdm2, and APC. Although not widely available in many laboratories, a panel of immunohistochemical markers may prove most useful as an adjunct in the evaluation of challenging parathyroid tumors.

Keywords

Parathyroid Parafibromin Parathyroid carcinoma Atypical parathyroid adenoma Parathyroid hormone Immunohistochemistry 

References

  1. 1.
    Rosai J, D.R., Carcangiu ML, Frable WJ, Tallini G, Tumors of the thyroid and parathyroid glands. AFIP Atlas of Tumor Pathology, ed. S. SG. Vol. Fascicle 21. 2014, Silver Spring, Maryland, USA: ARP Press. 606.Google Scholar
  2. 2.
    Tomita, T., Immunocytochemical staining patterns for parathyroid hormone and chromogranin in parathyroid hyperplasia, adenoma, and carcinoma. Endocr Pathol, 1999. 10(2): p. 145–156.CrossRefPubMedGoogle Scholar
  3. 3.
    Erickson, L.A., Jin L., Papotti M., Lloyd R.V., Oxyphil parathyroid carcinomas: a clinicopathologic and immunohistochemical study of 10 cases. Am J Surg Pathol, 2002. 26(3): p. 344–349.CrossRefPubMedGoogle Scholar
  4. 4.
    Gucer, H. and O. Mete, Endobronchial gangliocytic paraganglioma: not all keratin-positive endobronchial neuroendocrine neoplasms are pulmonary carcinoids. Endocr Pathol, 2014. 25(3): p. 356–358.CrossRefPubMedGoogle Scholar
  5. 5.
    Maeda, T., et al., A case of calcitonin-producing parathyroid adenoma with primary hyperparathyroidism. Jpn J Med, 1989. 28(5): p. 640–646.CrossRefPubMedGoogle Scholar
  6. 6.
    Chen, L., T.A. Dinh, and A. Haque, Small cell carcinoma of the ovary with hypercalcemia and ectopic parathyroid hormone production. Arch Pathol Lab Med, 2005. 129(4): p. 531–533.PubMedGoogle Scholar
  7. 7.
    Williamson, B.R., et al., Poorly differentiated lymphocytic lymphoma with ectopic parathormone production: visulization of metastatic calcification by bone scan. Clin Nucl Med, 1978. 3(10): p. 382–384.CrossRefPubMedGoogle Scholar
  8. 8.
    Holtz, G., T.R. Johnson, Jr., and M.E. Schrock, Paraneoplastic hypercalcemia in ovarian tumors. Obstet Gynecol, 1979. 54(4): p. 483–487.PubMedGoogle Scholar
  9. 9.
    Goldberg, R.S., D.B. Pilcher, and J.W. Yates, The aggressive surgical management of hypercalcemia due to ectopic parathormone production. Cancer, 1980. 45(10): p. 2652–2654.CrossRefPubMedGoogle Scholar
  10. 10.
    Max, M.H. and P.H. Lawrence, Ectopic secretion of parathyroid hormone. Surg Gynecol Obstet, 1980. 150(3): p. 411–418.PubMedGoogle Scholar
  11. 11.
    Patel, S. and J.T. Rosenthal, Hypercalcemia in carcinoma of prostate. Its cure by orchiectomy. Urology, 1985. 25(6): p. 627–629.CrossRefPubMedGoogle Scholar
  12. 12.
    Buller, R., Taylor K., Burg A.C., Berman M.L., DiSaia P.J., Paraneoplastic hypercalcemia associated with adenosquamous carcinoma of the endometrium. Gynecol Oncol, 1991. 40(1): p. 95–98.CrossRefPubMedGoogle Scholar
  13. 13.
    Nakajima, K., Tamai M., Okaniwa S., Nakamura Y., Kobayashi M., Niwa T., Horigome N., Ito N., Suzuki S., Nishio S., Komatsu M., Humoral hypercalcemia associated with gastric carcinoma secreting parathyroid hormone: a case report and review of the literature. Endocr J, 2013. 60(5): p. 557–562.CrossRefPubMedGoogle Scholar
  14. 14.
    Koyama, Y., Ishijima H., Ishibashi A., Katsuya T., Ishizaka H., Aoki J., Endo K., Intact PTH-producing hepatocellular carcinoma treated by transcatheter arterial embolization. Abdom Imaging, 1999. 24(2): p. 144–146.CrossRefPubMedGoogle Scholar
  15. 15.
    Oliveira, A.M., Tazelaar H.D., Myers J.L., Erickson L.A., Lloyd R.V., Thyroid transcription factor-1 distinguishes metastatic pulmonary from well-differentiated neuroendocrine tumors of other sites. Am J Surg Pathol, 2001. 25(6): p. 815–819.CrossRefPubMedGoogle Scholar
  16. 16.
    Agoff, S.N., Lamps L.W., Philip A.T., Amin M.B., Schmidt R.A., True L.D., Folpe A.L., Thyroid transcription factor-1 is expressed in extrapulmonary small cell carcinomas but not in other extrapulmonary neuroendocrine tumors. Mod Pathol, 2000. 13(3): p. 238–242.CrossRefPubMedGoogle Scholar
  17. 17.
    Kaufmann, O. and M. Dietel, Thyroid transcription factor-1 is the superior immunohistochemical marker for pulmonary adenocarcinomas and large cell carcinomas compared to surfactant proteins A and B. Histopathology, 2000. 36(1): p. 8–16.CrossRefPubMedGoogle Scholar
  18. 18.
    Folpe, A.L., Gown A.M., Lamps L.W., Garcia R., Dail D.H., Zarbo R.J., Schmidt R.A., Thyroid transcription factor-1: immunohistochemical evaluation in pulmonary neuroendocrine tumors. Mod Pathol, 1999. 12(1): p. 5–8.PubMedGoogle Scholar
  19. 19.
    Fabbro, D., di Loreto C., Stamerra O., Beltrami C.A., Lonigro R., Damante G., TTF-1 gene expression in human lung tumours. Eur J Cancer, 1996. 32A(3): p. 512–517.CrossRefPubMedGoogle Scholar
  20. 20.
    Bisceglia, M., Ragazzi M., Galliani C.A., Lastilla G., Rosai J., TTF-1 expression in nephroblastoma. Am J Surg Pathol, 2009. 33(3): p. 454–461.CrossRefPubMedGoogle Scholar
  21. 21.
    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): p. 192–200.CrossRefPubMedGoogle Scholar
  22. 22.
    Graham, A.D., A.R. Williams, and D.M. Salter, TTF-1 expression in primary ovarian epithelial neoplasia. Histopathology, 2006. 48(6): p. 764–765.CrossRefPubMedGoogle Scholar
  23. 23.
    Pratt, D., Afsar N., Allgauer M., Fetsch P., Palisoc M., Pittaluga S., Quezado M., Re-evaluating TTF-1 immunohistochemistry in diffuse gliomas: Expression is clonedependent and associated with tumor location. Clin Neuropathol, 2017, 36, 263, 271.CrossRefPubMedGoogle Scholar
  24. 24.
    Ni, Y.B., Tsang J.Y.S., Shao M.M., Chan S.K., Tong J., To K.F., Tse G.M., TTF-1 expression in breast carcinoma: an unusual but real phenomenon. Histopathology, 2014. 64(4): p. 504–511.CrossRefPubMedGoogle Scholar
  25. 25.
    Reis, H.G., et al., [TTF-1 (8G7G3/1) positive colon adenocarcinoma: diagnostic implications]. Pathologe, 2011. 32(4): p. 349–351.CrossRefPubMedGoogle Scholar
  26. 26.
    Hakim, S.A. and N.S. Youssef, Diagnostic Utility of Thyroid Transcription Factor-1 in Ovarian Carcinoma and Its Relationship With Clinicopathologic Prognostic Parameters. Appl Immunohistochem Mol Morphol, 2015.Google Scholar
  27. 27.
    Matoso, A., Singh K., Jacob R., Greaves W.O., Tavares R., Noble L., Resnick M.B., DeLellis R.A., Wang L.J., Comparison of thyroid transcription factor-1 expression by 2 monoclonal antibodies in pulmonary and nonpulmonary primary tumors. Appl Immunohistochem Mol Morphol, 2010. 18(2): p. 142–149.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Dettmer, M., Kim T.E., Jung C.K., Jung E.S., Lee K.Y., Kang C.S., Thyroid transcription factor-1 expression in colorectal adenocarcinomas. Pathol Res Pract, 2011. 207(11): p. 686–690.CrossRefPubMedGoogle Scholar
  29. 29.
    Erickson, L.A., Papouchado B., Dimashkieh H., Zhang S., Nakamura N., Lloyd R.V., Cdx2 as a marker for neuroendocrine tumors of unknown primary sites. Endocr Pathol, 2004. 15(3): p. 247–252.CrossRefPubMedGoogle Scholar
  30. 30.
    Marchiori, E., Pelizzo M.R., Herten M., Townsend D.M., Rubello D., Boschin I.M., Specifying the molecular pattern of sporadic parathyroid tumorigenesis-The Y282D variant of the GCM2 gene. Biomed Pharmacother, 2017. 92: p. 843–848.CrossRefPubMedGoogle Scholar
  31. 31.
    Nonaka, D., Study of parathyroid transcription factor Gcm2 expression in parathyroid lesions. Am J Surg Pathol, 2011. 35(1): p. 145–151.CrossRefPubMedGoogle Scholar
  32. 32.
    Guan, B., Welch J.M., Sapp J.C., Ling H., Li Y., Johnston J.J., Kebebew E., Biesecker L.G., Simonds W.F., Marx S.J., Agarwal S.K., GCM2-Activating Mutations in Familial Isolated Hyperparathyroidism. Am J Hum Genet, 2016. 99(5): p. 1034–1044.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Laury, A.R., Perets R., Piao H., Krane J.F., Barletta J.A., French C., Chirieac L.R., Lis R., Loda M., Hornick J.L., Drapkin R., Hirsch M.S., A comprehensive analysis of PAX8 expression in human epithelial tumors. Am J Surg Pathol, 2011. 35(6): p. 816–826.CrossRefPubMedGoogle Scholar
  34. 34.
    Ozcan, A., Shen S.S., Hamilton C., Anjana K., Coffey D., Krishnan B., Truong L.D., PAX 8 expression in non-neoplastic tissues, primary tumors, and metastatic tumors: a comprehensive immunohistochemical study. Mod Pathol, 2011. 24(6): p. 751–764.CrossRefPubMedGoogle Scholar
  35. 35.
    Bakshi, N., Kunju L.P., Giordano T., Shah R.B., Expression of renal cell carcinoma antigen (RCC) in renal epithelial and nonrenal tumors: diagnostic Implications. Appl Immunohistochem Mol Morphol, 2007. 15(3): p. 310–315.CrossRefPubMedGoogle Scholar
  36. 36.
    Han, S.I., Y. Tsunekage, and K. Kataoka, Gata3 cooperates with Gcm2 and MafB to activate parathyroid hormone gene expression by interacting with SP1. Mol Cell Endocrinol, 2015. 411: p. 113–120.CrossRefPubMedGoogle Scholar
  37. 37.
    Grigorieva, I.V. and R.V. Thakker, Transcription factors in parathyroid development: lessons from hypoparathyroid disorders. Ann N Y Acad Sci, 2011. 1237: p. 24–38.CrossRefPubMedGoogle Scholar
  38. 38.
    Grigorieva, I.V., Mirczuk S., Gaynor K.U., Nesbit M.A., Grigorieva E.F., Wei Q., Ali A., Fairclough R.J., Stacey J.M., Stechman M.J., Mihai R., Kurek D., Fraser W.D., Hough T., Condie B.G., Manley N., Grosveld F., Thakker R.V., Gata3-deficient mice develop parathyroid abnormalities due to dysregulation of the parathyroid-specific transcription factor Gcm2. J Clin Invest, 2010. 120(6): p. 2144–2155.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Miettinen, M., McCue P.A., Sarlomo-Rikala M., Rys J., Czapiewski P., Wazny K., Langfort R., Waloszczyk P., Biernat W., Lasota J., Wang Z., 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): p. 13–22.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Carpten, J.D., Robbins C.M., Villablanca A., Forsberg L., Presciuttini S., Bailey-Wilson J., Simonds W.F., Gillanders E.M., Kennedy A.M., Chen J.D., Agarwal S.K., Sood R., Jones M.P., Moses T.Y., Haven C., Petillo D., Leotlela P.D., Harding B., Cameron D., Pannett A.A., Höög A., Heath H., James-Newton L.A., Robinson B., Zarbo R.J., Cavaco B.M., Wassif W., Perrier N.D., Rosen I.B., Kristoffersson U., Turnpenny P.D., Farnebo L.O., Besser G.M., Jackson C.E., Morreau H., Trent J.M., Thakker R.V., Marx S.J., Teh B.T., Larsson C., Hobbs M.R., HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet, 2002. 32(4): p. 676–680.CrossRefPubMedGoogle Scholar
  41. 41.
    Hobbs, M.R., Pole A.R., Pidwirny G.N., Rosen I.B., Zarbo R.J., Coon H., Heath III H., Leppert M., Jackson C.E., Hyperparathyroidism-jaw tumor syndrome: the HRPT2 locus is within a 0.7-cM region on chromosome 1q. Am J Hum Genet, 1999. 64(2): p. 518–525.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Hendy, G.N. and D.E. Cole, Genetic defects associated with familial and sporadic hyperparathyroidism. Front Horm Res, 2013. 41: p. 149–165.CrossRefPubMedGoogle Scholar
  43. 43.
    Iacobone, M., et al., Parafibromin expression, single-gland involvement, and limited parathyroidectomy in familial isolated hyperparathyroidism. Surgery, 2007. 142(6): p. 984–991; discussion 984–91.CrossRefPubMedGoogle Scholar
  44. 44.
    Simonds, W.F., Robbins C.M., Agarwal S.K., Hendy G.N., Carpten J.D., Marx S.J., Familial isolated hyperparathyroidism is rarely caused by germline mutation in HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome. J Clin Endocrinol Metab, 2004. 89(1): p. 96–102.CrossRefPubMedGoogle Scholar
  45. 45.
    Teh, B.T., Farnebo F., Twigg S., Höög A., Kytölä S., Korpi-Hyövälti E., Wong F.K., Nordenström J., Grimelius L., Sandelin K., Robinson B., Farnebo L.O., Larsson C., Familial isolated hyperparathyroidism maps to the hyperparathyroidism-jaw tumor locus in 1q21-q32 in a subset of families. J Clin Endocrinol Metab, 1998. 83(6): p. 2114–2120.PubMedGoogle Scholar
  46. 46.
    Kelly, T.G., Shattuck T.M., Reyes-Mugica M., Stewart A.F., Simonds W.F., Udelsman R., Arnold A., Carpenter T.O., Surveillance for early detection of aggressive parathyroid disease: carcinoma and atypical adenoma in familial isolated hyperparathyroidism associated with a germline HRPT2 mutation. J Bone Miner Res, 2006. 21(10): p. 1666–1671.CrossRefPubMedGoogle Scholar
  47. 47.
    Szabo, J., et al., Hereditary hyperparathyroidism-jaw tumor syndrome: the endocrine tumor gene HRPT2 maps to chromosome 1q21-q31. Am J Hum Genet, 1995. 56(4): p. 944–950.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Yart, A., Gstaiger M., Wirbelauer C., Pecnik M., Anastasiou D., Hess D., Krek W., The HRPT2 tumor suppressor gene product parafibromin associates with human PAF1 and RNA polymerase II. Mol Cell Biol, 2005. 25(12): p. 5052–5060.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Woodard, G.E., Lin L., Zhang J.H., Agarwal S.K., Marx S.J., Simonds W.F., Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2, regulates cyclin D1/PRAD1 expression. Oncogene, 2005. 24(7): p. 1272–1276.CrossRefPubMedGoogle Scholar
  50. 50.
    Rozenblatt-Rosen, O., Hughes C.M., Nannepaga S.J., Shanmugam K.S., Copeland T.D., Guszczynski T., Resau J.H., Meyerson M., The parafibromin tumor suppressor protein is part of a human Paf1 complex. Mol Cell Biol, 2005. 25(2): p. 612–620.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Shattuck, T.M., Välimäki S., Obara T., Gaz R.D., Clark O.H., Shoback D., Wierman M.E., Tojo K., Robbins C.M., Carpten J.D., Farnebo L.O., Larsson C., Arnold A., Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med, 2003. 349(18): p. 1722–1729.CrossRefPubMedGoogle Scholar
  52. 52.
    Krebs, L.J., T.M. Shattuck, and A. Arnold, HRPT2 mutational analysis of typical sporadic parathyroid adenomas. J Clin Endocrinol Metab, 2005. 90(9): p. 5015–5017.CrossRefPubMedGoogle Scholar
  53. 53.
    Cetani, F., Pardi E., Borsari S., Viacava P., Dipollina G., Cianferotti L., Ambrogini E., Gazzerro E., Colussi G., Berti P., Miccoli P., Pinchera A., Marcocci C., Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors. J Clin Endocrinol Metab, 2004. 89(11): p. 5583–5591.CrossRefPubMedGoogle Scholar
  54. 54.
    Tan, M.H., Morrison C., Wang P., Yang X., Haven C.J., Zhang C., Zhao P., Tretiakova M.S., Korpi-Hyovalti E., Burgess J.R., Soo K.C., Cheah W.K., Cao B., Resau J., Morreau H., Teh B.T., Loss of parafibromin immunoreactivity is a distinguishing feature of parathyroid carcinoma. Clin Cancer Res, 2004. 10(19): p. 6629–6637.CrossRefPubMedGoogle Scholar
  55. 55.
    Gill, A.J., Clarkson A., Gimm O., Keil J., Dralle H., Howell V.M., Marsh D.J., Loss of nuclear expression of parafibromin distinguishes parathyroid carcinomas and hyperparathyroidism-jaw tumor (HPT-JT) syndrome-related adenomas from sporadic parathyroid adenomas and hyperplasias. Am J Surg Pathol, 2006. 30(9): p. 1140–9.CrossRefPubMedGoogle Scholar
  56. 56.
    Juhlin, C.C., Villablanca A., Sandelin K., Haglund F., Nordenstrom J., Forsberg L., Branstrom R., Obara T., Arnold A., Larsson C., Hoog A., Parafibromin immunoreactivity: its use as an additional diagnostic marker for parathyroid tumor classification. Endocr Relat Cancer, 2007. 14(2): p. 501–512.CrossRefPubMedGoogle Scholar
  57. 57.
    Cetani, F., Ambrogini E., Viacava P., Pardi E., Fanelli G., Naccarato A.G., Borsari S., Lemmi M., Berti P., Miccoli P., Pinchera A., Marcocci C., Should parafibromin staining replace HRTP2 gene analysis as an additional tool for histologic diagnosis of parathyroid carcinoma? Eur J Endocrinol, 2007. 156(5): p. 547–554.CrossRefPubMedGoogle Scholar
  58. 58.
    Fernandez-Ranvier, G.G., Khanafshar E., Tacha D., Wong M., Kebebew E., Duh Q.Y., Clark O.H., Defining a molecular phenotype for benign and malignant parathyroid tumors. Cancer, 2009. 115(2): p. 334–344.CrossRefPubMedGoogle Scholar
  59. 59.
    Juhlin, C.C., Nilsson I.L., Johansson K., Haglund F., Villablanca A., Höög A., Larsson C., Parafibromin and APC as screening markers for malignant potential in atypical parathyroid adenomas. Endocr Pathol, 2010. 21(3): p. 166–177.CrossRefPubMedGoogle Scholar
  60. 60.
    Kim, H.K., Oh Y.L., Kim S.H., Lee D.Y., Kang H.C., Lee J.I., Jang H.W., Hur K.Y., Kim J.H., Min Y.K., Chung J.H., Kim S.W., Parafibromin immunohistochemical staining to differentiate parathyroid carcinoma from parathyroid adenoma. Head Neck, 2012. 34(2): p. 201–206.CrossRefPubMedGoogle Scholar
  61. 61.
    Guarnieri, V., Battista C., Muscarella L.A., Bisceglia M., de Martino D., Baorda F., Maiello E., D’Agruma L., Chiodini I., Clemente C., Minisola S., Romagnoli E., Corbetta S., Viti R., Eller-Vainicher C., Spada A., Iacobellis M., Malavolta N., Carella M., Canaff L., Hendy G.N., Cole D.E.C., Scillitani A., CDC73 mutations and parafibromin immunohistochemistry in parathyroid tumors: clinical correlations in a single-centre patient cohort. Cell Oncol (Dordr), 2012. 35(6): p. 411–422.CrossRefPubMedGoogle Scholar
  62. 62.
    Wang, O., Wang C.Y., Shi J., Nie M., Xia W.B., Li M., Jiang Y., Guan H., Meng X.W., Xing X.P., Expression of Ki-67, galectin-3, fragile histidine triad, and parafibromin in malignant and benign parathyroid tumors. Chin Med J (Engl), 2012. 125(16): p. 2895–2901.Google Scholar
  63. 63.
    Truran, P.P., Johnson S.J., Bliss R.D., Lennard T.W.J., Aspinall S.R., Parafibromin, galectin-3, PGP9.5, Ki67, and cyclin D1: using an immunohistochemical panel to aid in the diagnosis of parathyroid cancer. World J Surg, 2014. 38(11): p. 2845–2854.CrossRefPubMedGoogle Scholar
  64. 64.
    Karaarslan, S., Yurum F.N., Kumbaraci B.S., Pala E.E., Sivrikoz O.N., Akyildiz M., Bugdayci M.H., The Role of Parafibromin, Galectin-3, HBME-1, and Ki-67 in the Differential Diagnosis of Parathyroid Tumors. Oman Med J, 2015. 30(6): p. 421–427.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Ryhanen, E.M., et al., A nationwide study on parathyroid carcinoma. Acta Oncol, 2017. 56(7): p. 991–1003.CrossRefPubMedGoogle Scholar
  66. 66.
    Cetani, F., Banti C., Pardi E., Borsari S., Viacava P., Miccoli P., Torregrossa L., Basolo F., Pelizzo M.R., Rugge M., Pennelli G., Gasparri G., Papotti M., Volante M., Vignali E., Saponaro F., Marcocci C., CDC73 mutational status and loss of parafibromin in the outcome of parathyroid cancer. Endocr Connect, 2013. 2(4): p. 186–195.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Howell, V.M., Gill A., Clarkson A., Nelson A.E., Dunne R., Delbridge L.W., Robinson B.G., Teh B.T., Gimm O., Marsh D.J., Accuracy of combined protein gene product 9.5 and parafibromin markers for immunohistochemical diagnosis of parathyroid carcinoma. J Clin Endocrinol Metab, 2009. 94(2): p. 434–441.CrossRefPubMedGoogle Scholar
  68. 68.
    Howell, V.M., Haven C.J., Kahnoski K., Khoo S.K., Petillo D., Chen J., Fleuren G.J., Robinson B.G., Delbridge L.W., Philips J., Nelson A.E., Krause U., Hammje K., Dralle H., Hoang-Vu C., Gimm O., Marsh D.J., Morreau H., Teh B.T., HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours. J Med Genet, 2003. 40(9): p. 657–663.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Juhlin, C., Larsson C., Yakoleva T., Leibiger I., Leibiger B., Alimov A., Weber G., Höög A., Villablanca A., Loss of parafibromin expression in a subset of parathyroid adenomas. Endocr Relat Cancer, 2006. 13(2): p. 509–523.CrossRefPubMedGoogle Scholar
  70. 70.
    Hu, Y., Liao Q., Cao S., Gao X., Zhao Y., Diagnostic performance of parafibromin immunohistochemical staining for sporadic parathyroid carcinoma: a meta-analysis. Endocrine, 2016. 54(3): p. 612–619.CrossRefPubMedGoogle Scholar
  71. 71.
    Tominaga, Y., Tsuzuki T., Matsuoka S., Uno N., Sato T., Shimabukuro S., Goto N., Nagasaka T., Uchida K., Expression of parafibromin in distant metastatic parathyroid tumors in patients with advanced secondary hyperparathyroidism due to chronic kidney disease. World J Surg, 2008. 32(5): p. 815–821.CrossRefPubMedGoogle Scholar
  72. 72.
    Hahn, M.A. and D.J. Marsh, Nucleolar localization of parafibromin is mediated by three nucleolar localization signals. FEBS Lett, 2007. 581(26): p. 5070–5074.CrossRefPubMedGoogle Scholar
  73. 73.
    Panicker, L.M., Zhang J.H., Dagur P.K., Gastinger M.J., Simonds W.F., Defective nucleolar localization and dominant interfering properties of a parafibromin L95P missense mutant causing the hyperparathyroidism-jaw tumor syndrome. Endocr Relat Cancer, 2010. 17(2): p. 513–524.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Juhlin, C.C., Haglund F., Obara T., Arnold A., Larsson C., Höög A., Absence of nucleolar parafibromin immunoreactivity in subsets of parathyroid malignant tumours. Virchows Arch, 2011. 459(1): p. 47–53.CrossRefPubMedGoogle Scholar
  75. 75.
    Kumari, N., Chaudhary N., Pradhan R., Agarwal A., Krishnani N., Role of Histological Criteria and Immunohistochemical Markers in Predicting Risk of Malignancy in Parathyroid Neoplasms. Endocr Pathol, 2016. 27(2): p. 87–96.CrossRefPubMedGoogle Scholar
  76. 76.
    Bergero, N., de Pompa R., Sacerdote C., Gasparri G., Volante M., Bussolati G., Papotti M., Galectin-3 expression in parathyroid carcinoma: immunohistochemical study of 26 cases. Hum Pathol, 2005. 36(8): p. 908–914.CrossRefPubMedGoogle Scholar
  77. 77.
    Ozolins, A., Narbuts Z., Vanags A., Simtniece Z., Visnevska Z., Akca A., Wirowski D., Gardovskis J., Strumfa I., Goretzki P.E., Evaluation of malignant parathyroid tumours in two European cohorts of patients with sporadic primary hyperparathyroidism. Langenbecks Arch Surg, 2016. 401(7): p. 943–951.CrossRefPubMedGoogle Scholar
  78. 78.
    Inic, Z., Inic M., Jancic S., Paunovic I., Tatic S., Tausanovic K., Zivavljevic V., Zegarac M., Inic I., Dunjdjerovic D., The relationship between proliferation activity and parathyroid hormone levels in parathyroid tumors. J BUON, 2015. 20(2): p. 562–566.PubMedGoogle Scholar
  79. 79.
    Lumachi, F., Ermani M., Marino F., Iacobone M., Baldessin M., Cappuzzo G., Zanella S., Favia G., PCNA-LII, Ki-67 immunostaining, p53 activity and histopathological variables in predicting the clinical outcome in patients with parathyroid carcinoma. Anticancer Res, 2006. 26(2A): p. 1305–1308.PubMedGoogle Scholar
  80. 80.
    Haven, C.J., van Puijenbroek M., Karperien M., Fleuren G.J., Morreau H., Differential expression of the calcium sensing receptor and combined loss of chromosomes 1q and 11q in parathyroid carcinoma. J Pathol, 2004. 202(1): p. 86–94.CrossRefPubMedGoogle Scholar
  81. 81.
    Stojadinovic, A., Hoos A., Nissan A., Dudas M.E., Cordon-Cardo C., Shaha A.R., Brennan M.F., Singh B., Ghossein R.A., Parathyroid neoplasms: clinical, histopathological, and tissue microarray-based molecular analysis. Hum Pathol, 2003. 34(1): p. 54–64.CrossRefPubMedGoogle Scholar
  82. 82.
    Kameyama, K., Takami H., Umemura S., Osamura Y.R., Wada N., Sugino K., Mimura T., Ito K., PCNA and Ki-67 as prognostic markers in human parathyroid carcinomas. Ann Surg Oncol, 2000. 7(4): p. 301–4.CrossRefPubMedGoogle Scholar
  83. 83.
    Dionisio, P., Stramignoni E., Passarino G., Pucci A., Valenti M., Berto I.M., Barbos P., Cadario A., Gasparri G., Bajardi P., Recurrent secondary hyperparathyroidism due to parathyroid carcinoma: usefulness of Ki-67 immunostaining in the diagnosis of a malignant parathyroid tumor. Nephron, 1996. 74(4): p. 720–723.CrossRefPubMedGoogle Scholar
  84. 84.
    Lloyd, R.V., Carney J.A., Ferreiro J.A., Jin L., Thompson G.B., van Heerden J.A., Grant C.S., Wollan P.C., Immunohistochemical Analysis of the Cell Cycle-Associated Antigens Ki-67 and Retinoblastoma Protein in Parathyroid Carcinomas and Adenomas. Endocr Pathol, 1995. 6(4): p. 279–287.CrossRefPubMedGoogle Scholar
  85. 85.
    Hosny Mohammed, K., et al., Parafibromin, APC, and MIB-1 Are Useful Markers for Distinguishing Parathyroid Carcinomas From Adenomas. Appl Immunohistochem Mol Morphol, 2016.Google Scholar
  86. 86.
    Saggiorato, E., Bergero N., Volante M., Bacillo E., Rosas R., Gasparri G., Orlandi F., Papotti M., Galectin-3 and Ki-67 expression in multiglandular parathyroid lesions. Am J Clin Pathol, 2006. 126(1): p. 59–66.CrossRefPubMedGoogle Scholar
  87. 87.
    Kruijff, S., Sidhu S.B., Sywak M.S., Gill A.J., Delbridge L.W., Negative parafibromin staining predicts malignant behavior in atypical parathyroid adenomas. Ann Surg Oncol, 2014. 21(2): p. 426–433.CrossRefPubMedGoogle Scholar
  88. 88.
    Erickson, L.A., Jalal S.M., Harwood A., Shearer B., Jin L., Lloyd R.V., Analysis of parathyroid neoplasms by interphase fluorescence in situ hybridization. Am J Surg Pathol, 2004. 28(5): p. 578–584.CrossRefPubMedGoogle Scholar
  89. 89.
    Hemmer, S., Wasenius V.M., Haglund C., Zhu Y., Knuutila S., Franssila K., Joensuu H., Deletion of 11q23 and cyclin D1 overexpression are frequent aberrations in parathyroid adenomas. Am J Pathol, 2001. 158(4): p. 1355–1362.CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Vasef, M.A., Brynes R.K., Sturm M., Bromley C., Robinson R.A., Expression of cyclin D1 in parathyroid carcinomas, adenomas, and hyperplasias: a paraffin immunohistochemical study. Mod Pathol, 1999. 12(4): p. 412–416.PubMedGoogle Scholar
  91. 91.
    Hsi, E.D., Zukerberg L.R., Yang W.I., Arnold A., Cyclin D1/PRAD1 expression in parathyroid adenomas: an immunohistochemical study. J Clin Endocrinol Metab, 1996. 81(5): p. 1736–1739.PubMedGoogle Scholar
  92. 92.
    Erovic, B.M., Harris L., Jamali M., Goldstein D.P., Irish J.C., Asa S.L., Mete O., Biomarkers of parathyroid carcinoma. Endocr Pathol, 2012. 23(4): p. 221–231.CrossRefPubMedGoogle Scholar
  93. 93.
    Arvai, K., et al., Molecular profiling of parathyroid hyperplasia, adenoma and carcinoma. Pathol Oncol Res, 2012. 18(3): p. 607–614.CrossRefPubMedGoogle Scholar
  94. 94.
    Osawa, N., Onoda N., Kawajiri H., Tezuka K., Takashima T., Ishikawa T., Miyauchi A., Hirokawa M., Wakasa K., Hirakawa K., Diagnosis of parathyroid carcinoma using immunohistochemical staining against hTERT. Int J Mol Med, 2009. 24(6): p. 733–741.PubMedGoogle Scholar
  95. 95.
    Dotzenrath, C., Teh B.T., Farnebo F., Cupisti K., Svensson A., Toell A., Goretzki P., Larsson C., Allelic loss of the retinoblastoma tumor suppressor gene: a marker for aggressive parathyroid tumors? J Clin Endocrinol Metab, 1996. 81(9): p. 3194–3196.CrossRefPubMedGoogle Scholar
  96. 96.
    Cryns, V.L., Thor A., Xu H.J., Hu S.X., Wierman M.E., Vickery Jr A.L., Benedict W.F., Arnold A., Loss of the retinoblastoma tumor-suppressor gene in parathyroid carcinoma. N Engl J Med, 1994. 330(11): p. 757–761.CrossRefPubMedGoogle Scholar
  97. 97.
    Shattuck, T.M., Kim T.S., Costa J., Yandell D.W., Imanishi Y., Palanisamy N., Gaz R.D., Shoback D., Clark O.H., Monchik J.M., Wierman M.E., Hollenberg A., Tojo K., Chaganti R.S.K., Arnold A., Mutational analyses of RB and BRCA2 as candidate tumour suppressor genes in parathyroid carcinoma. Clin Endocrinol (Oxf), 2003. 59(2): p. 180–189.CrossRefGoogle Scholar
  98. 98.
    Subramaniam, P., S. Wilkinson, and J.J. Shepherd, Inactivation of retinoblastoma gene in malignant parathyroid growths: a candidate genetic trigger? Aust N Z J Surg, 1995. 65(10): p. 714–716.CrossRefPubMedGoogle Scholar
  99. 99.
    Erickson, L.A., Jin L., Wollan P., Thompson G.B., van Heerden J.A., Lloyd R.V., Parathyroid hyperplasia, adenomas, and carcinomas: differential expression of p27Kip1 protein. Am J Surg Pathol, 1999. 23(3): p. 288–295.CrossRefPubMedGoogle Scholar
  100. 100.
    Witteveen, J.E., Hamdy N.A.T., Dekkers O.M., Kievit J., van Wezel T., Teh B.T., Romijn J.A., Morreau H., Downregulation of CASR expression and global loss of parafibromin staining are strong negative determinants of prognosis in parathyroid carcinoma. Mod Pathol, 2011. 24(5): p. 688–697.CrossRefPubMedGoogle Scholar
  101. 101.
    Duan, K., Mete, O., Familial Hyperparathyroidism Syndromes. Diagnostic Histopathology, 2016. 22(3): p. 92–100.CrossRefGoogle Scholar
  102. 102.
    Gill, A.J., Lim G., Cheung V.K.Y., Andrici J., Perry-Keene J.L., Paik J., Sioson L., Clarkson A., Sheen A., Luxford C., Elston M.S., Meyer-Rochow G.Y., Nano M.T., Kruijff S., Engelsman A.F., Sywak M., Sidhu S.B., Delbridge L.W., Robinson B.G., Marsh D.J., Toon C.W., Chou A., Clifton-Bligh R.J., Parafibromin-deficient (HPT-JT Type, CDC73 Mutated) Parathyroid Tumors Demonstrate Distinctive Morphologic Features. Am J Surg Pathol, 2018, 1.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA
  2. 2.Department of Pathology, Laboratory Medicine ProgramUniversity Health SystemTorontoCanada

Personalised recommendations