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Diagnostic performance of parafibromin immunohistochemical staining for sporadic parathyroid carcinoma: a meta-analysis

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Abstract

It is a challenge to distinguish parathyroid carcinoma (PTCA) from benign parathyroid lesions without recurrence or metastasis. Parafibromin immunohistochemical (IHC) staining had been described for the diagnosis of PTCA. But great variations existed in the reported sensitivity and specificity among different studies. We conducted a meta-analysis to summarize the diagnostic accuracy of parafibromin staining for PTCA. Published studies from Pubmed, Embase, and Cochrane Library were searched using the combination of terms “parafibromin,” “CDC73,” “HRPT2,” and “parathyroid.” Pooled sensitivity and specificity with 95 % confidence interval (CI) were calculated and the summary receiver operator characteristic (SROC) curves were constructed. The heterogeneity among included studies was evaluated and possible reasons were explored by meta-regression. A total of 10 studies including 202 patients with PTCA were finally enrolled in this meta-analysis. For parafibromin staining, sensitivity varied from 29 to 100 % (pooled estimate of 68 %; 95 % CI 49–82 %) and specificity ranged from 61 to 100 % (pooled estimate of 95 %; 95 % CI 85–98 %). The AUC for parafibromin staining was 0.91 (95 % CI 0.88–0.93). A significant heterogeneity was observed among included studies. According to meta-regression analysis, the scoring criteria and parafibromin antibody used in IHC were the covariates influencing the sensitivity. And the specificity decreased if atypical parathyroid adenomas were included in the control groups. The specificity of parafibromin staining was satisfactory for diagnosis of PTCA, while the sensitivity was limited. We suggested that a standardized IHC protocol and scoring system criteria should be applied in future studies to improve the diagnostic performance of parafibromin staining.

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References

  1. R.A. DeLellis, Parathyroid carcinoma: an overview. Adv. Anat. Pathol. 12(2), 53–61 (2005)

    Article  PubMed  Google Scholar 

  2. S. Brown, C. O’Neill, J. Suliburk, S. Sidhu, M. Sywak, A. Gill, B. Robinson, L. Delbridge, Parathyroid carcinoma: increasing incidence and changing presentation. ANZ J. Surg. 81(7–8), 528–532 (2011)

    Article  PubMed  Google Scholar 

  3. K. Sandelin, O. Tullgren, L.O. Farnebo, Clinical course of metastatic parathyroid cancer. World J. Surg. 18(4), 594–598 (1994)

    Article  CAS  PubMed  Google Scholar 

  4. G. Ippolito, F.F. Palazzo, F. Sebag, C. De Micco, J.F. Henry, Intraoperative diagnosis and treatment of parathyroid cancer and atypical parathyroid adenoma. Br. J. Surg. 94(5), 566–570 (2007)

    Article  CAS  PubMed  Google Scholar 

  5. E. Shane, Clinical review 122: parathyroid carcinoma. J. Clin. Endocrinol. Metab. 86(2), 485–493 (2001)

    Article  CAS  PubMed  Google Scholar 

  6. T. Obara, Y. Fujimoto, Diagnosis and treatment of patients with parathyroid carcinoma: an update and review. World J. Surg. 15(6), 738–744 (1991)

    Article  CAS  PubMed  Google Scholar 

  7. G. Favia, F. Lumachi, F. Polistina, D.F. D’Amico, Parathyroid carcinoma: sixteen new cases and suggestions for correct management. World J. Surg. 22(12), 1225–1230 (1998)

    Article  CAS  PubMed  Google Scholar 

  8. J.M. Sharretts, W.F. Simonds, Clinical and molecular genetics of parathyroid neoplasms. Best Pract. Res. Clin. Endocrinol. Metab. 24(3), 491–502 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. R.A. Delellis, Challenging lesions in the differential diagnosis of endocrine tumors: parathyroid carcinoma. Endocr. Pathol. 19(4), 221–225 (2008)

    Article  CAS  PubMed  Google Scholar 

  10. C. Dotzenrath, P.E. Goretzki, M. Sarbia, K. Cupisti, J. Feldkamp, H.D. Roher, Parathyroid carcinoma: problems in diagnosis and the need for radical surgery even in recurrent disease. Eur. J. Surg. Oncol. 27(4), 383–389 (2001)

    Article  CAS  PubMed  Google Scholar 

  11. M. Schaapveld, F.H. Jorna, K.K. Aben, H.R. Haak, J.T. Plukker, T.P. Links, Incidence and prognosis of parathyroid gland carcinoma: a population-based study in The Netherlands estimating the preoperative diagnosis. Am. J. Surg. 202(5), 590–597 (2011)

    Article  PubMed  Google Scholar 

  12. K.E. Levin, K.L. Chew, B.M. Ljung, B.H. Mayall, A.E. Siperstein, O.H. Clark, Deoxyribonucleic acid cytometry helps identify parathyroid carcinomas. J. Clin. Endocrinol. Metab. 67(4), 779–784 (1988)

    Article  CAS  PubMed  Google Scholar 

  13. J.D. Carpten, C.M. Robbins, A. Villablanca, L. Forsberg, S. Presciuttini, J. Bailey-Wilson, W.F. Simonds, E.M. Gillanders, A.M. Kennedy, J.D. Chen, S.K. Agarwal, R. Sood, M.P. Jones, T.Y. Moses, C. Haven, D. Petillo, P.D. Leotlela, B. Harding, D. Cameron, A.A. Pannett, A. Hoog, H.R. Heath, L.A. James-Newton, B. Robinson, R.J. Zarbo, B.M. Cavaco, W. Wassif, N.D. Perrier, I.B. Rosen, U. Kristoffersson, P.D. Turnpenny, L.O. Farnebo, G.M. Besser, C.E. Jackson, H. Morreau, J.M. Trent, R.V. Thakker, S.J. Marx, B.T. Teh, C. Larsson, M.R. Hobbs, HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat. Genet. 32(4), 676–680 (2002)

    Article  CAS  PubMed  Google Scholar 

  14. V.M. Howell, C.J. Haven, K. Kahnoski, S.K. Khoo, D. Petillo, J. Chen, G.J. Fleuren, B.G. Robinson, L.W. Delbridge, J. Philips, A.E. Nelson, U. Krause, K. Hammje, H. Dralle, C. Hoang-Vu, O. Gimm, D.J. Marsh, H. Morreau, B.T. Teh, HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours. J. Med. Genet. 40(9), 657–663 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. M.H. Tan, C. Morrison, P. Wang, X. Yang, C.J. Haven, C. Zhang, P. Zhao, M.S. Tretiakova, E. Korpi-Hyovalti, J.R. Burgess, K.C. Soo, W.K. Cheah, B. Cao, J. Resau, H. Morreau, B.T. Teh, Loss of parafibromin immunoreactivity is a distinguishing feature of parathyroid carcinoma. Clin. Cancer Res. 10(19), 6629–6637 (2004)

    Article  CAS  PubMed  Google Scholar 

  16. V.M. Howell, A. Gill, A. Clarkson, A.E. Nelson, R. Dunne, L.W. Delbridge, B.G. Robinson, B.T. Teh, O. Gimm, D.J. Marsh, Accuracy of combined protein gene product 9.5 and parafibromin markers for immunohistochemical diagnosis of parathyroid carcinoma. J. Clin. Endocrinol. Metab. 94(2), 434–441 (2009)

    Article  CAS  PubMed  Google Scholar 

  17. F. Cetani, E. Ambrogini, P. Viacava, E. Pardi, G. Fanelli, A.G. Naccarato, S. Borsari, M. Lemmi, P. Berti, P. Miccoli, A. Pinchera, C. Marcocci, Should parafibromin staining replace HRTP2 gene analysis as an additional tool for histologic diagnosis of parathyroid carcinoma? Eur. J. Endocrinol. 156(5), 547–554 (2007)

    Article  CAS  PubMed  Google Scholar 

  18. C.E. Quinn, J. Healy, A.H. Lebastchi, T.C. Brown, J.E. Stein, M.L. Prasad, G.G. Callender, T. Carling, R. Udelsman, Modern experience with aggressive parathyroid tumors in a high-volume New England referral center. J. Am. Coll. Surg. 220(6), 1054–1062 (2015)

    Article  PubMed  Google Scholar 

  19. P.F. Whiting, A.W. Rutjes, M.E. Westwood, S. Mallett, J.J. Deeks, J.B. Reitsma, M.M. Leeflang, J.A. Sterne, P.M. Bossuyt, QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann. Intern. Med. 155(8), 529–536 (2011)

    Article  PubMed  Google Scholar 

  20. J.P. Higgins, S.G. Thompson, J.J. Deeks, D.G. Altman, Measuring inconsistency in meta-analyses. BMJ 327(7414), 557–560 (2003)

    Article  PubMed  PubMed Central  Google Scholar 

  21. J.J. Deeks, P. Macaskill, L. Irwig, The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J. Clin. Epidemiol. 58(9), 882–893 (2005)

    Article  PubMed  Google Scholar 

  22. B. Littenberg, L.E. Moses, Estimating diagnostic accuracy from multiple conflicting reports: a new meta-analytic method. Med. Decis. Mak. 13(4), 313–321 (1993)

    Article  CAS  Google Scholar 

  23. G.G. Fernandez-Ranvier, E. Khanafshar, D. Tacha, M. Wong, E. Kebebew, Q.Y. Duh, O.H. Clark, Defining a molecular phenotype for benign and malignant parathyroid tumors. Cancer 115(2), 334–344 (2009)

    Article  PubMed  Google Scholar 

  24. C.C. Juhlin, F. Haglund, T. Obara, A. Arnold, C. Larsson, A. Hoog, Absence of nucleolar parafibromin immunoreactivity in subsets of parathyroid malignant tumours. Virchows Arch. 459(1), 47–53 (2011)

    Article  CAS  PubMed  Google Scholar 

  25. H.K. Kim, Y.L. Oh, S.H. Kim, D.Y. Lee, H.C. Kang, J.I. Lee, H.W. Jang, K.Y. Hur, J.H. Kim, Y.K. Min, J.H. Chung, S.W. Kim, Parafibromin immunohistochemical staining to differentiate parathyroid carcinoma from parathyroid adenoma. Head Neck 34(2), 201–206 (2012)

    Article  PubMed  Google Scholar 

  26. S. Kruijff, S.B. Sidhu, M.S. Sywak, A.J. Gill, L.W. Delbridge, Negative parafibromin staining predicts malignant behavior in atypical parathyroid adenomas. Ann. Surg. Oncol. 21(2), 426–433 (2014)

    Article  PubMed  Google Scholar 

  27. P.P. Truran, S.J. Johnson, R.D. Bliss, T.W. Lennard, S.R. Aspinall, Parafibromin, galectin-3, PGP9.5, Ki67, and cyclin D1: using an immunohistochemical panel to aid in the diagnosis of parathyroid cancer. World J. Surg. 38(11), 2845–2854 (2014)

    Article  PubMed  Google Scholar 

  28. V. Guarnieri, C. Battista, L.A. Muscarella, M. Bisceglia, D. de Martino, F. Baorda, E. Maiello, L. D’Agruma, I. Chiodini, C. Clemente, S. Minisola, E. Romagnoli, S. Corbetta, R. Viti, C. Eller-Vainicher, A. Spada, M. Iacobellis, N. Malavolta, M. Carella, L. Canaff, G.N. Hendy, D.E. Cole, A. Scillitani, CDC73 mutations and parafibromin immunohistochemistry in parathyroid tumors: clinical correlations in a single-centre patient cohort. Cell Oncol. (Dordr) 35(6), 411–422 (2012)

    Article  CAS  PubMed  Google Scholar 

  29. O. Wang, C. Wang, M. Nie, Q. Cui, H. Guan, Y. Jiang, M. Li, W. Xia, X. Meng, X. Xing, Novel HRPT2/CDC73 gene mutations and loss of expression of parafibromin in Chinese patients with clinically sporadic parathyroid carcinomas. PLoS ONE 7(9), e45567 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. C.C. Juhlin, A. Villablanca, K. Sandelin, F. Haglund, J. Nordenstrom, L. Forsberg, R. Branstrom, T. Obara, A. Arnold, C. Larsson, A. Hoog, Parafibromin immunoreactivity: its use as an additional diagnostic marker for parathyroid tumor classification. Endocr. Relat. Cancer 14(2), 501–512 (2007)

    Article  CAS  PubMed  Google Scholar 

  31. A.J. Gill, A. Clarkson, O. Gimm, J. Keil, H. Dralle, V.M. Howell, D.J. Marsh, 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. 30(9), 1140–1149 (2006)

    Article  PubMed  Google Scholar 

  32. G.Y. Meyer-Rochow, R. Alvarado, M.S. Sywak, S.B. Sidhu, L.W. Delbridge, A.J. Gill, Letter 2: intraoperative diagnosis and treatment of parathyroid cancer and atypical parathyroid adenoma (Br J Surg 2007; 94: 566–570). Br. J. Surg. 94(8), 1043–1044 (2007)

    Article  CAS  PubMed  Google Scholar 

  33. C. Juhlin, C. Larsson, T. Yakoleva, I. Leibiger, B. Leibiger, A. Alimov, G. Weber, A. Hoog, A. Villablanca, Loss of parafibromin expression in a subset of parathyroid adenomas. Endocr. Relat. Cancer 13(2), 509–523 (2006)

    Article  CAS  PubMed  Google Scholar 

  34. A.J. Gill, Understanding the genetic basis of parathyroid carcinoma. Endocr. Pathol. 25(1), 30–34 (2014)

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Yupei Zhao.

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Hu, Y., Liao, Q., Cao, S. et al. Diagnostic performance of parafibromin immunohistochemical staining for sporadic parathyroid carcinoma: a meta-analysis. Endocrine 54, 612–619 (2016). https://doi.org/10.1007/s12020-016-0997-3

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