Human Pathology
Volume 41, Issue 6 , Pages 805-814 , June 2010

Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes

  • Anthony J. Gill, FRCPA

      Affiliations

    • Department of Anatomical Pathology, Royal North Shore Hospital, Sydney 2065, Australia
    • University of Sydney, Sydney 2006, Australia
    • Corresponding Author InformationCorresponding author. Department of Anatomical Pathology, Royal North Shore Hospital, Pacific Highway, St Leonards, NSW 2065, Australia.
    • Dr Gill and Dr Benn contributed equally to this work.
    • ,
  • Diana E. Benn, PhD

      Affiliations

    • Cancer Genetics, Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, Sydney 2065, Australia
    • Dr Gill and Dr Benn contributed equally to this work.
    • ,
  • Angela Chou, FRCPA

      Affiliations

    • Department of Anatomical Pathology, Royal North Shore Hospital, Sydney 2065, Australia
    • ,
  • Adele Clarkson, BSc

      Affiliations

    • Department of Anatomical Pathology, Royal North Shore Hospital, Sydney 2065, Australia
    • ,
  • Anita Muljono, FRCPA

      Affiliations

    • Anatomical Pathology, Douglas Hanly Moir Pathology, Sydney 2113, Australia
    • ,
  • Goswin Y. Meyer-Rochow, FRACS

      Affiliations

    • Cancer Genetics, Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, Sydney 2065, Australia
    • Department of Surgery, Waikato Clinical School, Faculty of Medical and Health Sciences, University of Auckland 3240, New Zealand
    • ,
  • Anne Louise Richardson, BSc

      Affiliations

    • Cancer Genetics, Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, Sydney 2065, Australia
    • ,
  • Stan B. Sidhu, PhD

      Affiliations

    • Cancer Genetics, Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, Sydney 2065, Australia
    • University of Sydney, Department of Endocrine Surgery, Royal North Shore Hospital, Sydney 2065, Australia
    • ,
  • Bruce G. Robinson, MD

      Affiliations

    • Cancer Genetics, Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, Sydney 2065, Australia
    • ,
  • Roderick J. Clifton-Bligh, PhD

      Affiliations

    • Cancer Genetics, Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, Sydney 2065, Australia

Received 9 November 2009 ,Revised 1 December 2009 ,Accepted 2 December 2009.

References 

  1. Baysal BE. Hereditary paraganglioma targets diverse paraganglia. J Med Genet. 2002;39:617–622
  2. In:  DeLellis RA,  Lloyd RV,  Heitz RV,  Heng C editor. World Health Organization Classification of Tumours Pathology and Genetics of Tumours of Endocrine Organs. Lyon: IARC Press; 2004;p. 147–166
  3. Lenders JW, Eisenhofer G, Mannelli M, Pacak K. Phaeochromocytoma. Lancet. 2005;366:665–675
  4. Neumann HP, Eng C. The approach to the patient with paraganglioma. J Clin Endocrinol Metab. 2009;94:2677–2683
  5. Komminoth P, Perren A, van Nederveen F, de Krijger RR. Familial endocrine tumours: phaeochromocytomas and extra-adrenal paragangliomas. Diagn Histopathol. 2009;2:61–68
  6. van Nederveen FH, Gaal J, Favier J, et al. An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC or SDHD gene mutations: a retrospective and prospective analysis. Lancet Oncol. 2009;8:764–771
  7. Hao HX, Khalimonchuk O, Schraders M, et al. SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science. 2009;325:1139–1142
  8. Korpershoek E, van Nederveen FH, Dannenberg H, et al. Genetic analysis of apparently sporadic pheochromocytomas: the Rotterdam Experience. Ann N Y Acad Sci. 2006;1073:138–148
  9. Baysal BE, Ferrell RE, Willett-Brozick JE, et al. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science. 2000;287:848–851
  10. Benn DE, Gimenez-Roqueplo AP, Reilly JR, et al. Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. J Clin Endocrinol Metab. 2006;91:827–836
  11. Neumann HP, Pawlu C, Peczkowska M. Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. JAMA. 2004;292:943–951
  12. Schiavi F, Boedeker CC, Bausch B, et al. Predictors and prevalence of paraganglioma syndrome associated with mutations of the SDHC gene. JAMA. 2005;294:2057–2063
  13. Amar L, Bertherat J, Baudin E, et al. Genetic testing in pheochromocytoma or functional paraganglioma. J Clin Oncol. 2005;23:8812–8818
  14. van Nederveen FH, Korpershoek E, Lenders JW, et al. Somatic SDHB mutation in extraadrenal pheochromocytoma. N Engl J Med. 2007;357:306
  15. Bolland M, Benn D, Croxson M, et al. Gastrointestinal stromal tumour in succinate dehydrogenase subunit B mutation-associated familial phaeochromocytoma/paraganglioma. ANZ J Surg. 2006;76:763–764
  16. Ricketts C, Woodward ER, Killick P, et al. Germline SDHB mutations and familial renal cell carcinoma. J Natl Cancer Inst. 2008;100:1260–1262
  17. Vanharanta S, Buchta M, McWhinney SR, et al. Early-onset renal cell carcinoma as a novel extraparaganglial component of SDHB-associated heritable paraganglioma. Am J Hum Genet. 2004;74:153–159
  18. Bayley JP, van Minderhout I, Weiss MM, et al. Mutation analysis of SDHB and SDHC novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma. BMC Med Genet. 2006;7:1
  19. Gimm O, Armanios M, Dziema H, et al. Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial phaeochromocytoma. Cancer Res. 2000;60:6822–6825
  20. Benn D, Robinson B. Genetic basis of phaeochromocytoma and paraganglioma. Best Pract Res Clin Endocrinol Metab. 2006;20:435–450
  21. Neumann HP, Bausc B, McWhinney SR, et al. Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med. 2002;346:1459–1466
  22. Bornstein SR, Gimenez-Roqueplo AP. Genetic testing in pheochromocytoma: increasing importance for clinical decision making. Ann N Y Acad Sci. 2006;1073:94–103
  23. Gimenez-Roqueplo AP, Lehnert H, et al. Phaeochromocytoma, new genes and screening strategies. Clin Endocrinol (Oxf). 2006;65:699
  24. Pacak K, Eisenhofer G, Ahlman H, et al. Phaeochromocytoma: recommendations for clinical practice From the First International symposium. Nat Clin Pract Endocrinol Metab. 2007;3:92–102
  25. Burnichon N, Rohmer V, Amar L, et al. The succinate dehydrogenase genetic testing in a large prospective series of patients with paraganglioma. J Clin Endocrinol Metab. 2009;94:2817–2827
  26. Meyer-Rochow GY, Smith JM, Richardson AL, et al. Denaturing high performance liquid chromatography detection of SDHB, SDHD and VHL germline mutations in pheochromocytoma. J Surg Res. 2009;157:55–62
  27. Neumann HP, Erlic Z, Boedeker C, et al. Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall out. Cancer Res. 2009;69:3650–3656
  28. Benn D, Croxson M, Tucker K, et al. Novel succinate dehydrogenase subunit B (SDHB) mutations in familial phaeochromocytomas and paragangliomas, but an absence of somatic SDHB mutations in sporadic phaeochromocytomas. Oncogene. 2003;22:1358–1364
  29. Marsh D, Theodosopoulos G, Howell V, et al. Rapid mutation scanning of genes associated with familial cancer syndromes using denaturing high-performance liquid chromatography. Neoplasia. 2001;3:236–244
  30. Dannenberg H, Dinjens SNM, Abbou M, et al. Frequent germ-line succinate dehydrogenase subunit D gene mutations in patients with apparently sporadic parasympathetic paraganglia. Clin Cancer Res. 2002;8:2061–2066
  31. Gottlieb E, Tomlinson IP. Mitochondrial tumour suppressors: a genetic and biochemical update. Nat Rev. 2005;857–866
  32. Eng C, Kiuru M, Fernandez M, Aaltonin L. A role for mitochondrial enzymes in inherited neoplasia and beyond. Nat Rev Cancer. 2003;3:193–2002
  33. Gimenez-Roqueplo AP, Favier J, Rustin P, et al. The R22X mutation of the SDHD gene in hereditary paraganglioma abolishes the enzymatic activity of complex II in the mitochondrial respiratory chain and activates the hypoxia pathway. Am J Hum Genet. 2001;69:1186–1197
  34. Gimenez-Roqueplo AP, Favier J, Rustin P. Functional consequences of SDHB gene mutation in an apparently sporadic phaeochromocytoma. J Clin Endocrinol Metab. 2002;87:4771–4774
  35. Pasini B, McWhinney SR, Bei T, et al. Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC and SDHD. Eur J Hum Genet. 2008;16:79–88
  36. Douwes-Dekker PBM, Hogendoorn PC, Kuipers-Dijkshoorn N, et al. SDHD mutations in head and neck paragangliomas result in destabilization of complex II in the mitochondrial respiratory chain with loss of enzymatic activity and abnormal mitochondrial morphology. J Pathol. 2003;201:480–486
  37. Dahia PLM, Ross KN, Wright ME, et al. A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas. PLoS Genet. 2005;1:72–80
  38. Ladroue C, Carcenac R, Leporrier M, et al. PHD2 mutation and congenital erythrocytosis with paraganglioma. N Engl J Med. 2008;359:2685–2692
  39. Pollard PJ, Ratcliffe PJ. Puzzling patterns of cancer predisposition. Science. 2009;324:192–194
  40. Lindor NM, Petersen GM, Hadley DW, et al. Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA. 2006;296:1507–1517
  41. Gill AJ, Clarkson A, Gimm O, et al. Loss of nuclear expression of parafibromin distinguishes parathyroid carcinomas and hyperparathyroidsim–jaw tumor (HPT-JT) syndrome related adenomas from sporadic parathyroid adenomas and hyperplasias. Am J Surg Pathol. 2006;30:1140–1149
  42. Howell VM, Gill AJ, Clarkson A, et al. Accuracy of combined protein gene product 9.5 and parafibromin markers for immunohistochemical diagnosis of parathyroid carcinoma. J Clin Endocrinol Metab. 2009;94:434–441
  43. www.rcpa.edu.au/static/File/Asset%20library/public%20documents/Policy%20Manual/Position%20Statements/Consent%20for%20performing%20MSI%20and%20IHC%20pre-screening%20for%20HNPCC.pdf [accessed October 4 2009].

PII: S0046-8177(09)00456-0

doi: 10.1016/j.humpath.2009.12.005

Human Pathology
Volume 41, Issue 6 , Pages 805-814 , June 2010

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