Diagnostic tests and biomarkers for pheochromocytoma and extra-adrenal paraganglioma: From routine laboratory methods to disease stratification

Endocrine Pathology

Volumn 23, Issue 1, 2012, Pages 4-14

  Eisenhofer, Graeme ^a   Tischler, Arthur S ^b   De Krijger, Ronald R ^c  

^a DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^b TUFTS MEDICAL CENTER   (United States)

^c ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

Biomarkers; Catecholamines; Diagnosis; Dopamine; Metanephrines; Methoxytyramine; Paraganglioma; Pheochromocytoma; SDHB

Indexed keywords

BIOLOGICAL MARKER; CATECHOLAMINE; GRANIN DERIVED PEPTIDE; MESSENGER RNA; PEPTIDE; SUCCINATE DEHYDROGENASE; UNCLASSIFIED DRUG;

BENIGN TUMOR; CHEMICAL ANALYSIS; DIAGNOSTIC TEST; DISEASE CLASSIFICATION; ENZYME SUBUNIT; EXTRA ADRENAL PARAGANGLIOMA; GENE EXPRESSION; GENETIC SCREENING; GENOTYPE; HEREDITY; HISTOPATHOLOGY; HUMAN; IMMUNOHISTOCHEMISTRY; LABORATORY TEST; METASTASIS; METASTASIS POTENTIAL; MUTATION; PARAGANGLIOMA; PATIENT CODING; PHEOCHROMOCYTOMA; PHEOCHROMOCYTOMA OF THE ADRENAL GLAND SCALED SCORE; PREDICTION; PRIORITY JOURNAL; PROTEOMICS; REVIEW; SCORING SYSTEM; TRANSCRIPTOMICS;

ADRENAL GLAND NEOPLASMS; HUMANS; PARAGANGLIOMA, EXTRA-ADRENAL; PHEOCHROMOCYTOMA; TUMOR MARKERS, BIOLOGICAL;

EID: 84858705443     PISSN: 10463976     EISSN: 15590097     Source Type: Journal    
DOI: 10.1007/s12022-011-9188-1     Document Type: Review

References (98)

1. Eisenhofer G, Goldstein DS, Kopin IJ, Crout JR: Pheochromocytoma: rediscovery as a catecholamine-metabolizing tumor. Endocr Pathol 14:193-212, 2003
2. Eisenhofer G, Kopin IJ, Goldstein DS: Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev 56:331-49, 2004 (Pubitemid 39096594)
3. Eisenhofer G, Lenders JW, Linehan WM, Walther MM, Goldstein DS, Keiser HR: Plasma normetanephrine and metanephrine for detecting pheochromocytoma in von Hippel - Lindau disease and multiple endocrine neoplasia type 2.N Engl JMed 340:1872-9, 1999 (Pubitemid 29272667)
4. Lenders JW, Pacak K, Walther MM, et al.: Biochemical diagnosis of pheochromocytoma: which test is best? Jama 287:1427-34, 2002 (Pubitemid 34250506)
5. Pacak K, Eisenhofer G, Ahlman H, et al.: Pheochromocytoma: recommendations for clinical practice from the First International Symposium. Nat Clin Pract Endocrinol Metab 3:92-102, 2007 (Pubitemid 46146962)
6. Raber W, Raffesberg W, Bischof M, et al.: Diagnostic efficacy of unconjugated plasma metanephrines for the detection of pheochromocytoma. Arch Intern Med 160:2957-63, 2000 (Pubitemid 32009053)
7. Sawka AM, Jaeschke R, Singh RJ, Young WF, Jr.: A comparison of biochemical tests for pheochromocytoma: Measurement of fractionated plasma metanephrines compared with the combination of 24-hour urinary metanephrines and catecholamines. J Clin Endocrinol Metab 88:553-8, 2003 (Pubitemid 36207789)
8. Unger N, Pitt C, Schmidt IL, et al.: Diagnostic value of various biochemical parameters for the diagnosis of pheochromocytoma in patients with adrenal mass. Eur J Endocrinol 154:409-17, 2006
9. Vaclavik J, Stejskal D, Lacnak B, et al.: Free plasma metanephrines as a screening test for pheochromocytoma in low-risk patients. J Hypertens 25:1427-31, 2007 (Pubitemid 46918830)
10. Hickman PE, Leong M, Chang J, Wilson SR, McWhinney B: Plasma free metanephrines are superior to urine and plasma catecholamines and urine catecholamine metabolites for the investigation of phaeochromocytoma. Pathology 41:173-7, 2009
11. Gao YC, Lu HK, Luo QY, Chen LB, Ding Y, Zhu RS: Comparison of free plasma metanephrines enzyme immunoassay with (131)IMIBG scan in diagnosis of pheochromocytoma. Clin Exp Med 8:87-91, 2008 (Pubitemid 351999727)
12. Sarathi V, Pandit R, Jagtap V, et al.: Performance of fractionated plasma free metanephrines by enzyme immunoassay in the diagnosis of pheochromocytoma and paraganglioma. Endocr Pract 17:759-65, 2011
13. Marney LC, Laha TJ, Baird GS, Rainey PM, Hoofnagle AN: Isopropanol protein precipitation for the analysis of plasma free metanephrines by liquid chromatography-tandem mass spectrometry. Clin Chem 54:1729-32, 2008
14. Whiting MJ: Simultaneous measurement of urinary metanephrines and catecholamines by liquid chromatography with tandem mass spectrometric detection. Ann Clin Biochem 46:129-36, 2009
15. Peaston RT, Graham KS, Chambers E, van der Molen JC, Ball S: Performance of plasma free metanephrines measured by liquid chromatography-tandem mass spectrometry in the diagnosis of pheochromocytoma. Clin Chim Acta 411:546-52, 2010
16. Marrington R, Johnston J, Knowles S, Webster C: Measurement of urinary metadrenaline and normetadrenaline by liquid chromatography tandem mass spectrometry for the diagnosis of phaeochromocytoma. Ann Clin Biochem 47:467-75, 2010
17. Gabler J, Miller A, Wang S: A simple liquid chromatographytandem mass spectrometry method for measuring metanephrine and normetanephrine in urine. Clin Chem Lab Med 49:1213-6, 2011
18. He X, Gabler J, Yuan C, Wang S, Shi Y, Kozak M: Quantitative measurement of plasma free metanephrines by ion-pairing solid phase extraction and liquid chromatography-tandem mass spectrometry with porous graphitic carbon column. J Chromatogr B Analyt Technol Biomed Life Sci 879:2355-9, 2011
19. Pillai D, Ross HA, Kratzsch J, et al.: Proficiency test of plasma free and total metanephrines: report from a study group. Clin Chem Lab Med 47:786-90, 2009
20. Pillai D, Callen S: Pilot quality assurance programme for plasma metanephrines. Ann Clin Biochem 47:137-42, 2010
21. Mullins F, O'Shea P, Fitzgerald R, Tormey W: Enzyme-linked immunoassay for plasma-free metanephrines in the biochemical diagnosis of phaeochromocytoma in adults is not ideal. Clin Chem Lab Med 2011 (in press)
22. Boyle JG, Davidson DF, Perry CG, Connell JM: Comparison of diagnostic accuracy of urinary free metanephrines VMA, and catecholamines and plasma catecholamines for diagnosis of pheochromocytoma. J Clin Endocrinol Metab 92:4602-8, 2007 (Pubitemid 350223433)
23. Douwes Dekker PB, Corver WE, Hogendoorn PC, van der Mey AG, Cornelisse CJ: Multiparameter DNA flow-sorting demonstrates diploidy and SDHD wild-type gene retention in the sustentacular cell compartment of head and neck paragangliomas: chief cells are the only neoplastic component. J Pathol 202:456-62, 2004 (Pubitemid 38456164)
24. Tischler AS: Pheochromocytoma: time to stamp out "malignancy"? Endocr Pathol 19:207-8, 2008
25. Linnoila RI, Keiser HR, Steinberg SM, Lack EE: Histopathology of benign versus malignant sympathoadrenal paragangliomas: clinicopathologic study of 120 cases including unusual histologic features. Hum Pathol 21:1168-80, 1990 (Pubitemid 20382001)
26. Kimura N, Watanabe T, Noshiro T, Shizawa S, Miura Y: Histological grading of adrenal and extra-adrenal pheochromocytomas and relationship to prognosis: a clinicopathological analysis of 116 adrenal pheochromocytomas and 30 extra-adrenal sympathetic paragangliomas including 38 malignant tumors. Endocr Pathol 16:23-32, 2005 (Pubitemid 41278311)
27. Thompson LD: Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases. Am J Surg Pathol 26:551-66, 2002
28. Gao B, Meng F, Bian W, et al.: Development and validation of pheochromocytoma of the adrenal gland scaled score for predicting malignant pheochromocytomas. Urology 68:282-6, 2006 (Pubitemid 44175483)
29. Strong VE, Kennedy T, Al-Ahmadie H, et al.: Prognostic indicators of malignancy in adrenal pheochromocytomas: clinical, histopathologic, and cell cycle/apoptosis gene expression analysis. Surgery 143:759-68, 2008
30. Wu D, Tischler AS, Lloyd RV, et al.: Observer variation in the application of the Pheochromocytoma of the Adrenal Gland Scaled Score. Am J Surg Pathol 33:599-608, 2009
31. Agarwal A, Mehrotra PK, Jain M, et al.: Size of the tumor and pheochromocytoma of the adrenal gland scaled score (PASS): can they predict malignancy? World J Surg 34:3022-8, 2010
32. Favier J, Plouin PF, Corvol P, Gasc JM: Angiogenesis and vascular architecture in pheochromocytomas: distinctive traits in malignant tumors. Am J Pathol 161:1235-46, 2002
33. Eisenhofer G, Lenders JW, Siegert G, et al.: Plasma methoxytyramine: a novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumor size, location and SDHB mutation status. Eur J Cancer 2011 (in press)
34. Remine W, Chong G, van Heerden J, Sheps S, Harrison EJ: Current management of pheochromocytoma. Ann Surg 179:740-8, 1974
35. Shen WT, Sturgeon C, Clark OH, Duh QY, Kebebew E: Should pheochromocytoma size influence surgical approach? A comparison of 90 malignant and 60 benign pheochromocytomas. Surgery 136:1129-37, 2004 (Pubitemid 39647525)
36. van der Harst E, Bruining HA, Jaap Bonjer H, et al.: Proliferative index in phaeochromocytomas: does it predict the occurrence of metastases? J Pathol 191:175-80, 2000 (Pubitemid 30394896)
37. Ayala-Ramirez M, Feng L, Johnson MM, et al.: Clinical risk factors for malignancy and overall survival in patients with pheochromocytomas and sympathetic paragangliomas: primary tumor size and primary tumor location as prognostic indicators. J Clin Endocrinol Metab 96:717-25, 2011
38. Feng F, Zhu Y, Wang X, et al.: Predictive factors for malignant pheochromocytoma: analysis of 136 patients. J Urol 185:1583-90, 2011
39. John H, Ziegler WH, Hauri D, Jaeger P: Pheochromocytomas: can malignant potential be predicted? Urology 53:679-83, 1999 (Pubitemid 29163029)
40. Park J, Song C, Park M, et al.: Predictive characteristics of malignant pheochromocytoma. Korean J Urol 52:241-6, 2011
41. Clarke MR,Weyant RJ,Watson CG, Carty SE: Prognostic markers in pheochromocytoma. Hum Pathol 29:522-6, 1998 (Pubitemid 28213474)
42. Medeiros LJ, Wolf BC, Balogh K, Federman M: Adrenal pheochromocytoma: a clinicopathologic review of 60 cases. Hum Pathol 16:580-9, 1985 (Pubitemid 15049632)
43. Plouin PF, Chatellier G, Fofol I, Corvol P: Tumor recurrence and hypertension persistence after successful pheochromocytoma operation. Hypertension 29:1133-9, 1997 (Pubitemid 27198222)
44. Proye C, Vix M, Goropoulos A, Kerlo P, Lecomte-Houcke M: High incidence of malignant pheochromocytoma in a surgical unit. 26 cases out of 100 patients operated from 1971 to 1991. J Endocrinol Invest 15:651-63, 1992
45. Goldstein RE, O'Neill JA, Jr., Holcomb GW, 3rd, et al.: Clinical experience over 48 years with pheochromocytoma. Ann Surg 229:755-64; discussion 64-6, 1999
46. Mannelli M, Ianni L, Cilotti A, Conti A: Pheochromocytoma in Italy: a multicentric retrospective study. Eur J Endocrinol 141:619-24, 1999 (Pubitemid 30064762)
47. Edstrom Elder E, Hjelm Skog AL, Hoog A, Hamberger B: The management of benign and malignant pheochromocytoma and abdominal paraganglioma. Eur J Surg Oncol 29:278-83, 2003 (Pubitemid 36395565)
48. Amar L, Servais A, Gimenez-Roqueplo AP, Zinzindohoue F, Chatellier G, Plouin PF: Year of diagnosis, features at presentation, and risk of recurrence in patients with pheochromocytoma or secreting paraganglioma. J Clin Endocrinol Metab 90:2110-6, 2005 (Pubitemid 40586247)
49. Chapman DB, Lippert D, Geer CP, et al.: Clinical, histopathologic, and radiographic indicators of malignancy in head and neck paragangliomas. Otolaryngol Head Neck Surg 143:531-7, 2010
50. Ghayee HK, Havekes B, Corssmit EP, et al.: Mediastinal paragangliomas: association with mutations in the succinate dehydrogenase genes and aggressive behavior. Endocr Relat Cancer 16:291-9, 2009
51. Amar L, Bertherat J, Baudin E, et al.: Genetic testing in pheochromocytoma or functional paraganglioma. J Clin Oncol 23:8812-8, 2005 (Pubitemid 46211527)
52. Brouwers FM, Eisenhofer G, Tao JJ, et al.: High frequency of SDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: implications for genetic testing. J Clin Endocrinol Metab 91:4505-9, 2006 (Pubitemid 44833431)
53. Ricketts CJ, Forman JR, Rattenberry E, et al.: Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD. Hum Mutat 31:41-51, 2010
54. King KS, Prodanov T, Kantorovich V, et al.: Metastatic Pheochromocytoma/paraganglioma related to primary tumor development in childhood or adolescence: significant link to SDHB mutations. J Clin Oncol 29:4137-42, 2011
55. Eisenhofer G, Huynh TT, Pacak K, et al.: Distinct gene expression profiles in norepinephrine- and epinephrine-producing hereditary and sporadic pheochromocytomas: activation of hypoxia-driven angiogenic pathways in von Hippel - Lindau syndrome. Endocrine-Related Cancer 11:897-911, 2004 (Pubitemid 40065561)
56. Dahia PL, Ross KN, Wright ME, et al.: A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas. PLoS Genet 1:72-80, 2005
57. Favier J, Briere JJ, Burnichon N, et al.: The Warburg effect is genetically determined in inherited pheochromocytomas. PLoS One 4:e7094, 2009
58. Lopez-Jimenez E, Gomez-Lopez G, Leandro-Garcia LJ, et al.: Research resource: Transcriptional profiling reveals different pseudohypoxic signatures in SDHB and VHL-related pheochromocytomas. Mol Endocrinol 24:2382-91, 2010
59. Burnichon N, Vescovo L, Amar L, et al.: Integrative genomic analysis reveals somatic mutations in pheochromocytoma and paraganglioma. Hum Mol Genet 20:3974-3985, 2011
60. Eisenhofer G, Lenders JW, Timmers H, et al.: Measurements of plasma methoxytyramine, normetanephrine, and metanephrine as discriminators of different hereditary forms of pheochromocytoma. Clin Chem 57:411-20, 2011
61. Eisenhofer G, Pacak K, Huynh TT, et al.: Catecholamine metabolomic and secretory phenotypes in phaeochromocytoma. Endocr Relat Cancer 18:97-111, 2011
62. Eisenhofer G, Timmers H, Lenders JW, et al.: Age at diagnosis of pheochromocytoma differs according to catecholamine phenotype and tumor location. Journal of Clinical Endocrinology and Metabolism 96:375-84, 2011
63. Robinson R, Smith P, Whittaker SR: Secretion of catecholamines in malignant phaeochromocytoma. Br Med J 1:1422-4, 1964
64. Tippett PA, McEwan AJ, Ackery DM: A re-evaluation of dopamine excretion in phaeochromocytoma. Clin Endocrinol (Oxf) 25:401-10, 1986 (Pubitemid 16031777)
65. Rao F, Keiser HR, O'Connor DT: Malignant pheochromocytoma. Chromaffin granule transmitters and response to treatment. Hypertension 36:1045-52, 2000
66. Januszewicz W, Wocial B, Januszewicz A, Gryglas P, Prejbisz A: Dopamine and dopa urinary excretion in patients with pheochromocytoma - diagnostic implications. Blood Press 10:212-6, 2001 (Pubitemid 33149901)
67. van der Harst E, de Herder WW, de Krijger RR, et al.: The value of plasma markers for the clinical behaviour of phaeochromocytomas. Eur J Endocrinol 147:85-94, 2002 (Pubitemid 34814744)
68. Yon L, Guillemot J, Montero-Hadjadje M, et al.: Identification of the secretogranin II-derived peptide EM66 in pheochromocytomas as a potential marker for discriminating benign versus malignant tumors. J Clin Endocrinol Metab 88:2579-85, 2003 (Pubitemid 36724427)
69. Guerin M, Guillemot J, Thouennon E, et al.: Granins and their derived peptides in normal and tumoral chromaffin tissue: implications for the diagnosis and prognosis of pheochromocytoma. Regul Pept 165:21-9, 2010
70. Szalat A, Fraenkel M, Doviner V, Salmon A, Gross DJ: Malignant pheochromocytoma: predictive factors of malignancy and clinical course in 16 patients at a single tertiary medical center. Endocrine 39:160-6, 2011
71. Timmers HJ, Pacak K, Huynh TT, et al.: Biochemically silent abdominal paragangliomas in patients with mutations in the Sdhb Gene. J Clin Endocrinol Metab 93:4826-4832, 2008
72. Eisenhofer G, Lenders JW, Goldstein DS, et al.: Pheochromocytoma catecholamine phenotypes and prediction of tumor size and location by use of plasma free metanephrines. Clin Chem 51:735-44, 2005 (Pubitemid 40463925)
73. 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 10:764-71, 2009
74. Korpershoek E, Favier J, Gaal J, et al.: SDHA immunohistochemistry detects germline SDHA gene mutations in apparently sporadic paragangliomas and pheochromocytomas. J Clin Endocrinol Metab 96:E1472-6, 2011
75. Gill AJ, Benn DE, Chou A, et al.: Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes. Hum Pathol 41:805-14, 2010
76. Gill AJ, Chou A, Vilain R, et al.: Immunohistochemistry for SDHB divides gastrointestinal stromal tumors (GISTs) into 2 distinct types. Am J Surg Pathol 34:636-44, 2011
77. Gaal J, Stratakis CA, Carney JA, et al.: SDHB immunohistochemistry: a useful tool in the diagnosis of Carney - Stratakis and Carney triad gastrointestinal stromal tumors. Mod Pathol 24:147-51, 2011
78. Janeway KA, Kim SY, Lodish M, et al.: Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proc Natl Acad Sci U S A 108:314-8, 2011
79. Miettinen M,Wang ZF, Sarlomo-Rikala M, Osuch C, Rutkowski P, Lasota J: Succinate dehydrogenase-deficient GISTs: a clinicopathologic, immunohistochemical, and molecular genetic study of 66 gastric GISTs with predilection to young age. Am J Surg Pathol 35:1712-21, 2011
80. Gill AJ, Chou A, Vilain RE, Clifton-Bligh RJ: "Pediatric- type"gastrointestinal stromal tumors are SDHB negative ("type 2") GISTs. Am J Surg Pathol 35:1245-7; author reply 7-8, 2011
81. Gill AJ, Pachter NS, Clarkson A, et al.: Renal tumors and hereditary pheochromocytoma-paraganglioma syndrome type 4. N Engl J Med 364:885-6, 2011
82. Gill AJ, Pachter NS, Chou A, et al.: Renal tumors associated with germline SDHB mutation show distinctive morphology. Am J Surg Pathol 35:1578-85, 2011
83. Sandgren J, Andersson R, Rada-Iglesias A, et al.: Integrative epigenomic and genomic analysis of malignant pheochromocytoma. Exp Mol Med 42:484-502, 2010
84. Brouwers FM, Petricoin EF, 3rd, Ksinantova L, et al.: Low molecular weight proteomic information distinguishes metastatic from benign pheochromocytoma. Endocr Relat Cancer 12:263-72, 2005 (Pubitemid 40896445)
85. Brouwers FM, Elkahloun AG, Munson PJ, et al.: Gene expression profiling of benign and malignant pheochromocytoma. Ann N Y Acad Sci 1073:541-56, 2006 (Pubitemid 44912049)
86. Suh I, Shibru D, Eisenhofer G, et al.: Candidate genes associated with malignant pheochromocytomas by genome-wide expression profiling. Ann Surg 250:983-90, 2009
87. Bjorklund P, Cupisti K, Fryknas M, et al.: Stathmin as a marker for malignancy in pheochromocytomas. Exp Clin Endocrinol Diabetes 118:27-30, 2010
88. Thouennon E, Pierre A, Tanguy Y, et al.: Expression of trophic amidated peptides and their receptors in benign and malignant pheochromocytomas: high expression of adrenomedullin RDC1 receptor and implication in tumoral cell survival. Endocr Relat Cancer 17:637-51, 2010
89. Waldmann J, Fendrich V, Holler J, et al.: Microarray analysis reveals differential expression of benign and malignant pheochromocytoma. Endocr Relat Cancer 17:743-56, 2010
90. Thouennon E, Elkahloun AG, Guillemot J, et al.: Identification of potential gene markers and insights into the pathophysiology of pheochromocytoma malignancy. J Clin Endocrinol Metab 92:4865-72, 2007 (Pubitemid 350223470)
91. Eisenhofer G, Bornstein SR, Brouwers FM, et al.: Malignant pheochromocytoma: current status and initiatives for future progress. Endocr Relat Cancer 11:423-36, 2004 (Pubitemid 39331275)
92. Chrisoulidou A, Kaltsas G, Ilias I, Grossman AB: The diagnosis and management of malignant phaeochromocytoma and paraganglioma. Endocr Relat Cancer 14:569-85, 2007 (Pubitemid 350074048)
93. Tombol Z, Eder K, Kovacs A, et al.: MicroRNA expression profiling in benign (sporadic and hereditary) and recurring adrenal pheochromocytomas. Mod Pathol 23:1583-95, 2010
94. Meyer-Rochow GY, Jackson NE, Conaglen JV, et al.: MicroRNA profiling of benign and malignant pheochromocytomas identifies novel diagnostic and therapeutic targets. Endocr Relat Cancer 17:835-46, 2010
95. Grossman A, Pacak K, Sawka A, et al.: Biochemical diagnosis and localization of pheochromocytoma: can we reach a consensus? Ann N Y Acad Sci 1073:332-47, 2006 (Pubitemid 44912029)
96. Michaud GY: The role of standards in the development and implementation of clinical laboratory tests: a domestic and global perspective. Cancer Biomark 1:209-16, 2005
97. Hall JA, Brown R, Paul J: An exploration into study design for biomarker identification: issues and recommendations. Cancer Genomics Proteomics 4:111-9, 2007
98. Mischak H, Allmaier G, Apweiler R, et al.: Recommendations for biomarker identification and qualification in clinical proteomics. Sci Transl Med 2:46ps2, 2010