Genetic and epigenetic differences of benign and malignant pheochromocytomas and paragangliomas (PPGLs)

Open access

Abstract

Pheochromocytomas and paragangliomas (PPGLs) are tumors arising from the adrenal medulla and sympathetic/parasympathetic paraganglia, respectively. According to Th e Cancer Genome Atlas (TCGA), approximately 40% of PPGLs are due to germ line mutations in one of 16 susceptibility genes, and a further 30% are due to somatic alterations in at least seven main genes (VHL, EPAS1, CSDE1, MAX, HRAS, NF1, RET, and possibly KIF1B). Th e diagnosis of malignant PPGL was straight forward in most cases as it was defined as presence of PPGL in non-chromaffin tissues. Accordingly, there is an extreme need for new diagnostic marker(s) to identify tumors with malignant prospective. Th e aim of this study was to review all suggested genetic and epigenetic alterations that are remarkably different between benign and malignant PPGLs. It seems that more than two genetic mutation clusters in PPGLs and other genetic and methylation biomarkers could be targeted for malignancy discrimination in different studies.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • Agarwal SK Guru SC Heppner C Erdos MR Collins RM Park SY Saggar S Chandrasekharappa SC Collins FS Spiegel AM Marx SJ Burns AL. Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription. Cell 96 143-152 1999.

  • Akerstrom G . Introduction to symposium: ‘New genetics with impact on treatment of endocrine tumour disease’. J Intern Med 280 536-539 2016.

  • Amar L Bertherat J Baudin E Ajzenberg C Bressac-de Paillerets B Chabre O Chamontin B Delemer B Giraud S Murat A Niccoli-Sire P Richard S Rohmer V Sadoul JL Strompf L Schlumberger M Bertagna X Plouin PF Jeunemaitre X Gimenez-Roqueplo AP. Genetic testing in pheochromocytoma or functional paraganglioma. J Clin Oncol 23 8812-8818 2005.

  • Amar L Baudin E Burnichon N Peyrard S Silvera S Bertherat J Bertagna X Schlumberger M Jeunemaitre X Gimenez-Roqueplo AP Plouin PF. Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas. J Clin Endocrinol Metab 92 3822-3828 2007.

  • Amousha MRH Sabetkish N Heshmat R Rajabiani A Saff ar H Haghpanah V Tavangar SM. Expression of the pituitary tumor transforming gene (PTTG1) in pheochromocytoma as a potential marker for distinguishing benign versus malignant tumors. Acta Med Iran 53 236-241 2015.

  • Assadipour Y Sadowski SM Alimchandani M Quezado M Steinberg SM Nilubol N Patel D Prodanov T Pacak K Kebebew E. SDHB mutation status and tumor size but not tumor grade are important predictors of clinical outcome in pheochromocytoma and abdominal paraganglioma. Surgery 161 230-239 2017.

  • Backman S Crona J Maharjan R Stalberg P Hellman P Bjorklund P. Global promoter methylation analysis identifi es malignant pheochromocytomas. Meeting Abstracts Adrenal Tumors Glucocorticoid Regulation and Action Endocrine Society’s 97th Annual Meeting and Expo FRI-358 2015.

  • Backman S Maharjan R Falk-Delgado A Crona J Cupisti K Stalberg P Hellman P Bjorklund P. Global DNA Methylation Analysis Identifi es Two Discrete clusters of Pheochromocytoma with Distinct Genomic and Genetic Alterations. Sci Rep 7 44943 2017.

  • Bayley JP Kunst HP Cascon A Sampietro ML Gaal J Korpershoek E Hinojar-Gutierrez A Timmers HJ Hoefsloot LH Hermsen MA Suarez C Hussain AK Vriends AH Hes FJ Jansen JC Tops CM Corssmit EP de Knijff P Lenders JW Cremers CW Devilee P Dinjens WN de Krijger RR Robledo M. SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma. Lancet Oncol 11 366-372 2010.

  • Baysal BE Willett-Brozick JE Lawrence EC Drovdlic CM Savul SA McLeod DR Yee HA Brackmann DE Slattery WH 3rd Myers EN Ferrell RE Rubinstein WS. Prevalence of SDHB SDHC and SDHD germline mutations in clinic patients with head and neck paragangliomas. J Med Genet 39 178-183 2002.

  • Boltze C Mundschenk J Unger N Schneider-Stock R Peters B Mawrin C Hoang-Vu C Roessner A Lehnert H. Expression profi le of the telomeric complex discriminates between benign and malignant pheochromocytoma. J Clin Endocrinol Metab 88 4280-4286 2003.

  • Boron WF Boulpaep EL. (Eds.) Medical Physiology: A Cellular and Molecular Approach. Saunders 2009.

  • Brouwers FM Elkahloun AG Munson PJ Eisenhofer G Barb J Linehan WM Lenders JW De Krijger R Mannelli M Udelsman R Ocal IT Shulkin BL Bornstein SR Breza J Ksinantova L Pacak K. Gene expression profi ling of benign and malignant pheochromocytoma. Ann N Y Acad Sci 1073 541-556 2006.

  • Bryant J Farmer J Kessler LJ Townsend RR Nathanson KL. Pheochromocytoma: the expanding genetic diff erential diagnosis. J Natl Cancer Inst 95 1196-1204 2003.

  • Burnichon N Cascon A Schiavi F Morales NP Comino-Mendez I Abermil N et al. MAX mutations cause hereditary and sporadic pheochromocytoma and paraganglioma. Clin Cancer Res 18 2828-2837 2012.

  • Burnichon N Buff et A Gimenez-Roqueplo AP. Pheochromocytoma and paraganglioma: molecular testing and personalized medicine. Curr Opin Oncol 28 5-10 2016.

  • Capelli P Martignoni G Pedica F Falconi M Antonello D Malpeli G Scarpa A. Endocrine neoplasms of the pancreas: pathologic and genetic features. Arch Pathol Lab Med 133 350-364 2009.

  • Castro-Vega LJ Buff et A De Cubas AA Cascon A Menara M Khalifa E Amar L Azriel S Bourdeau I Chabre O Curras-Freixes M Franco-Vidal V Guillaud-Bataille M Simian C Morin A Leton R Gomez-Grana A Pollard PJ Rustin P Robledo M Favier J Gimenez-Roqueplo AP. Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas. Hum Mol Genet 23 2440-2446 2014.

  • Chen H Sippel RS O’Dorisio MS Vinik AI Lloyd RV Pacak K; North American Neuroendocrine Tumor Society (NANETS). Th e North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: pheochromocytoma paraganglioma and medullary thyroid cancer. Pancreas 39 775-783 2010.

  • Comino-Mendez I Gracia-Aznarez FJ Schiavi F Landa I Leandro-Garcia LJ Leton R Honrado E Ramos-Medina R Caronia D Pita G Gomez-Grana A de Cubas AA Inglada-Perez L Maliszewska A Taschin E Bobisse S Pica G Loli P Hernandez-Lavado R Diaz JA Gomez-Morales M Gonzalez-Neira A Roncador G Rodriguez-Antona C Benitez J Mannelli M Opocher G Robledo M Cascon A. Exome sequencing identifi es MAX mutations as a cause of hereditary pheochromocytoma. Nat Genet 43 663-667 2011.

  • Cwikla JB Bodei L Kolasinska-Cwikla A Sankowski A Modlin IM Kidd M. Circulating transcript analysis (NETest) in GEP-NETs treated with somatostatin analogs defi nes therapy. J Clin Endocrinol Metab 100 E1437-E1445 2015.

  • Dahia PL Ross KN Wright ME Hayashida CY Santagata S Barontini M Kung AL Sanso G Powers JF Tischler AS Hodin R Heitritter S Moore F Dluhy R Sosa JA Ocal IT Benn DE Marsh DJ Robinson BG Schneider K Garber J Arum SM Korbonits M Grossman A Pigny P Toledo SP Nose V Li C Stiles CD. A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas. PLoS Genet 1 72-80 200 5.

  • Dahia PL. Pheochromocytoma and paraganglioma pathogenesis: learning from genetic heterogeneity. Nat Rev Cancer 14 108-119 2014.

  • Darr R Lenders JW Hofb auer LC Naumann B Bornstein SR Eisenhofer G. Pheochromocytoma - update on disease management. Th er Adv Endocrinol Metab 3 11-26 2012.

  • de Cubas AA Korpershoek E Inglada-Perez L Letouze E Curras-Freixes M Fernandez AF Comino-Mendez I Schiavi F Mancikova V Eisenhofer G Mannelli M Opocher G Timmers H Beuschlein F de Krijger R Cascon A Rodriguez-Antona C Fraga MF Favier J Gimenez-Roqueplo AP Robledo M. DNA methylation profiling in pheochromocytoma and paraganglioma reveals diagnostic and prognostic markers. Clin Cancer Res 21 3020-3030 2015.

  • DeLellis RA Lloyd RV H eitz PU Eng C. (Eds.): World Health Organization Classifi cation of Tumours. Pathology and Genetics of Tumours of Endocrine Organs. IARC Press: Lyon 2004.

  • Eisenhofer G Kopin IJ Goldstein DS. Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev 56 331-349 2004a.

  • Eisenhofer G Bornstein SR Brouwers FM Cheung NK Dahia PL de Krijger RR Giordano TJ Greene LA Goldstein DS Lehnert H Manger WM Maris JM Neumann HP Pacak K Shulkin BL Smith DI Tischler AS Young WF Jr. Malignant pheochromocytoma: current status and initiatives for future progress. Endocr Relat Cancer 11 423-436 2004b.

  • Elder EE Xu D Hoog A Enberg U Hou M Pisa P Gruber A Larsson C Backdahl M. KI-67 AND hTERT expression can aid in the distinction between malignant and benign pheochromocytoma and paraganglioma. Mod Pathol 16 246-255 2003.

  • Favier J Plouin PF Cor vol P Gasc JM. Angiogenesis and vascular architecture in pheochromocytomas: distinctive traits in malignant tumors. Am J Pathol 161 1235-1246 2002.

  • Favier J Gimenez-Roquep lo AP. Pheochromocytomas: the (pseudo)-hypoxia hypothesis. Best Pract Res Clin Endocrinol Metab 24 957-968 2010.

  • Favier J Gimenez-Roquep lo AP. [Genetics of paragangliomas and pheochromocytomas]. Med Sci (Paris) 28 625- 632 2012.

  • Favier J Amar L Gimene z-Roqueplo AP. Paraganglioma and phaeochromocytoma: from genetics to personalized medicine. Nat Rev Endocrinol 11 101-111 2015.

  • Fishbein L Merrill S F raker DL Cohen DL Nathanson KL. Inherited mutations in pheochromocytoma and paraganglioma: why all patients should be off ered genetic testing. Ann Surg Oncol 20 1444-1450 2013.

  • Fishbein L Khare S Wubbenhorst B DeSloover D D’Andrea K Merrill S Cho NW Greenberg RA Else T Montone K LiVolsi V Fraker D Daber R Cohen DL Nathanson KL. Whole-exome sequencing identifi es somatic ATRX mutations in pheochromocytomas and paragangliomas. Nat Commun 6 6140 2015.

  • Fishbein L. Pheochromocy toma and paraganglioma: genetics diagnosis and treatment. Hematol Oncol Clin North Am 30 135-150 2016.

  • Fishbein L Leshchiner I Walter V Danilova L Robertson AG Johnson A et al. Abstract 4371: Integrated molecular characterization of pheochromocytoma and paraganglioma including a novel recurrent and prognostic fusion gene. Cancer Research 76 4371 2016.

  • Fishbein L Leshchiner I Walter V Danilova L Robertson AG Johnson AR et al. Comprehensive molecular characterization of pheochromocytoma and paraganglioma. Cancer Cell 31 181-193 2017.

  • Galan SR Kann PH. Genet ics and molecular pathogenesis of pheochromocytoma and paraganglioma. Clin Endocrinol (Oxf) 78 165-175 2013.

  • Geli J Kiss N Lanner F Foukakis T Natalishvili N Larsson O Kogner P Hoog A Clark GJ Ekstrom TJ Backdahl M Farnebo F Larsson C. Th e Ras eff ectors NORE1A and RASSF1A are frequently inactivated in pheochromocytoma and abdominal paraganglioma. Endocr Relat Cancer 14 125-134 2007.

  • Gimenez-Roqueplo AP. Gen etics of paragangliomas and pheochromocytoma. Abstracts for the Ninth International Workshop on Multiple Endocrine Neoplasia (MEN2004) Journal of Internal Medicine 255 703 2004.

  • Gimenez-Roqueplo AP Dah ia PL Robledo M. An update on the genetics of paraganglioma pheochromocytoma and associated hereditary syndromes. Horm Metab Res 44 328-333 2012.

  • Giubellino A Sourbier C Lee MJ Scroggins B Bullova P Landau M Ying W Neckers L Trepel JB Pacak K. Targeting heat shock protein 90 for the treatment of malignant pheochromocytoma. PLoS One 8 e56083 2013.

  • Guo Z Lloyd RV. Pheochr omocytomas and paragangliomas: an update on recent molecular genetic advances and criteria for malignancy. Adv Anat Pathol 22 283-293 2015.

  • Haghpanah V Shooshtariz adeh P Heshmat R Larijani B Tavangar SM. Immunohistochemical analysis of survivin expression in thyroid follicular adenoma and carcinoma. Appl Immunohistochem Mol Morphol 14 422-425 2006.

  • Hasani-Ranjbar S1 Amoli MM Ebrahim-Habibi A Haghpanah V Hejazi M Soltani A Larijani B. Mutation screening of VHL gene in a family with malignant bilateral pheochromocytoma: from isolated familial pheochromocytoma to von Hippel-Lindau disease. Fam Cancer 8 465-471 2009.

  • Hasani-Ranjbar S Amoli MM Ebrahim-Habibi A Gozashti MH Khalili N Sayyahpour FA Hafeziyeh J Soltani A Larijani B. A new frameshift MEN1 gene mutation associated with familial malignant insulinomas. Fam Cancer 10 343-348 2011.

  • Helman LJ Cohen PS Averbuch SD Cooper MJ Keiser HR Israel MA. Neuropeptide Y expression distinguishes malignant from benign pheochromocytoma. J Clin Oncol 7 1720-1725 1989.

  • Jones PA. DNA methylatio n and cancer. Cancer Res 46 461-466 1986.

  • Juhlin CC Stenman A Ha glund F Clark VE Brown TC Baranoski J Bilguvar K Goh G Welander J Svahn F Rubinstein JC Caramuta S Yasuno K Gunel M Backdahl M Gimm O Soderkvist P Prasad ML Korah R Lift on RP Carling T. Whole‐exome sequencing defi nes the mutational landscape of pheochromocytoma and identifi es KMT2D as a recurrently mutated gene. Genes Chromosomes Cancer 54 542-554 2015.

  • Kajbafzadeh AM Payabvash S Salmasi AH Monajemzadeh M Tavangar SM. Smooth muscle cell apoptosis and defective neural development in congenital ureteropelvic junction obstruction. J Urol 176 718-723 2006.

  • Khatami F Noorinayer B Ghiasi S Mohebi R Hashemi M Zali MR. Lack of eff ects of single nucleotide polymorphisms of the DNA methyltransferase 1 gene on gastric cancer in Iranian patients: a case control study. Asian Pac J Cancer Prev 10 1177-1182 2009a.

  • Khatami F Noorinayer B Mohebi SR Ghiasi S Mohebi R Hashemi M Zali MR. Eff ects of amino acid substitution polymorphisms of two DNA methyltransferases on susceptibility to sporadic colorectal cancer. Asian Pac J Cancer Prev 10 1183-1188 2009b.

  • Khatami F Tavangar SM. Current diagnostic status of pheochromocytoma and future perspective: A mini review. Iran J Pathol 12 313-322 2017.

  • Khatami F Larijani B Ta vangar SM Circulating tumor BRAF mutation and personalized thyroid cancer treatment. Asian Pac J Cancer Prev 18 293-294 2017a.

  • Khatami F Aghayan HR Sanaei M Heshmat R Tavangar SM Larijani B. Th e potential of circulating tumor cells in personalized management of breast cancer: A systematic review. Acta Med Iran 55 175-193 2017b.

  • Kidd M Drozdov I Modlin I. Blood and tissue neuroendocrine tumor gene cluster analysis correlate defi ne hallmarks and predict disease status. Endocr Relat Cancer 22 561-575 2015.

  • Kimura N Takayanagi R T akizawa N Itagaki E Katabami T Kakoi N Rakugi H Ikeda Y Tanabe A Nigawara T Ito S Kimura I Naruse M; Phaeochromocytoma Study Group in Japan. Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma. Endocr Relat Cancer 21 405-414 2014.

  • Kleihues P Louis DN Sch eithauer BW Rorke LB Reifenberger G Burger PC Cavenee WK. Th e WHO classifi cation of tumors of the nervous system. J Neuropathol Exp Neurol 61 215-229 2002.

  • Kouros-Mehr H Slorach EM Sternlicht MD Werb Z. GATA-3 maintains the diff erentiation of the luminal cell fate in the mammary gland. Cell 127 1041-1055 2006.

  • Larijani B Shirzad M Mo hagheghi MA Haghpanah V Mosavi-Jarrahi AR Tavangar SM Vassigh AR Hossein-Nezhad A Bandarian F Baradar-Jalili R. Epidemiologic analysis of the Tehran cancer institute data system registry (TCIDSR). Asian Pac J Cancer Prev 5 36-39 2004.

  • Lee S Nakamura E Yang H Wei W Linggi MS Sajan MP Farese RV Freeman RS Carter BD Kaelin WG Jr Schlisio S. Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: developmental culling and cancer. Cancer Cell 8 155-167 2005.

  • Letouze E Martinelli C Loriot C Burnichon N Abermil N Ottolenghi C Janin M Menara M Nguyen AT Benit P Buff et A Marcaillou C Bertherat J Amar L Rustin P De Reynies A Gimenez-Roqueplo AP Favier J. SDH mutations establish a hypermethylator phenotype in paraganglioma. Cancer Cell 23 739-752 2013.

  • Li SC Essaghir A Martij n C Lloyd RV Demoulin JB Oberg K Giandomenico V. Global microRNA profi ling of well-diff erentiated small intestinal neuroendocrine tumors. Mod Pathol 26 685-696 2013.

  • Linnoila RI Keiser HR S teinberg SM Lack EE. Histopathology of benign versus malignant sympathoadrenal paragangliomas: clinicopathologic study of 120 cases including unusual histologic features. Hum Pathol 21 1168-1180 1990.

  • Lopez-Jimenez E Gomez-Lo pez G Leandro-Garcia LJ Munoz I Schiavi F Montero-Conde C de Cubas AA Ramires R Landa I Leskela S Maliszewska A Inglada-Perez L de la Vega L Rodriguez-Antona C Leton R Bernal C de Campos JM Diez-Tascon C Fraga MF Boullosa C Pisano DG Opocher G Robledo M Cascon A. Research resource: transcriptional profi ling reveals diff erent pseudohypoxic signatures in SDHB and VHLrelated pheochromocytomas. Mol Endocrinol 24 2382-2391 2010.

  • Majidi M Haghpanah V He dayati M Khashayar P Mohajeri-Tehrani MR Larijani B. A family presenting with multiple endocrine neoplasia type 2B: A case report. J Med Case Rep 5 587 2011.

  • Mannelli M Castellano M Schiavi F Filetti S Giacche M Mori L Pignataro V Bernini G Giache V Bacca A Biondi B Corona G Di Trapani G Grossrubatscher E Reimondo G Arnaldi G Giacchetti G Veglio F Loli P Colao A Ambrosio MR Terzolo M Letizia C Ercolino T Opocher G; Italian heochromocytoma/Paraganglioma Network. Clinically guided genetic screening in a large cohort of italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas. J Clin Endocrinol Metab 94 1541-1547 2009.

  • Margetts CD Morris M As tuti D Gentle DC Cascon A McRonald FE Catchpoole D Robledo M Neumann HP Latif F Maher ER. Evaluation of a functional epigenetic approach to identify promoter region methylation in phaeochromocytoma and neuroblastoma. Endocr Relat Cancer 15 777-786 2008.

  • McNeil AR Blok BH Koelm eyer TD Burke MP Hilton JM. Phaeochromocytomas discovered during coronial autopsies in Sydney Melbourne and Auckland. Aust N Z J Med 30 648-652 2000.

  • Modlin IM Frilling A Sa lem RR Alaimo D Drymousis P Wasan HS Callahan S Faiz O Weng L Teixeira N Bodei L Drozdov I Kidd M. Blood measurement of neuroendocrine gene transcripts defi nes the eff ectiveness of operative resection and ablation strategies. Surgery 159 336-347 2016.

  • Mohammadi-asl J Larijani B Khorgami Z Tavangar SM Haghpanah V Kheirollahi M Mehdipour P. Qualitative and quantitative promoter hypermethylation patterns of the P16 TSHR RASSF1A and RARβ2 genes in papillary thyroid carcinoma. Med Oncol 28 1123-1128 2011.

  • Mulukutla SN Rednam SP Pl on SE Balazs AE. SUN-005: Th e role of genetics in pheochromocytoma/paraganglioma. Pediatrics-Case Reports II (posters). Endocrine Society’s 98th Annual Meeting and Expo April 1-4 2016 Boston.

  • Muscarella P Bloomston M Brewer AR Mahajan A Frankel WL Ellison EC Farrar WB Weghorst CM Li J. Expression of the p16INK4A/Cdkn2a gene is prevalently downregulated in human pheochromocytoma tumor specimens. Gene Expr 14 207-216 2008.

  • Nasseri-Moghaddam S Malekz adeh R Sotoudeh M Tavangar M Azimi K Sohrabpour AA Mostadjabi P Fathi H Minapoor M. Lower esophagus in dyspeptic Iranian patients: a prospective study. J Gastroenterol Hepatol 18 315-321 2003.

  • Neumann HP Bausch B McWhi nney SR Bender BU Gimm O Franke G Schipper J Klisch J Altehoefer C Zerres K Januszewicz A Eng C Smith WM Munk R Manz T Glaesker S Apel TW Treier M Reineke M Walz MK Hoang-Vu C Brauckhoff M Klein-Franke A Klose P Schmidt H Maier-Woelfl e M Peczkowska M Szmigielski C Eng C; Freiburg-Warsaw-Columbus Pheochromocytoma Study Group. Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med 346 1459-1466 2002.

  • Nolting S Grossman AB. Sign aling pathways in pheochromocytomas and paragangliomas: prospects for future therapies. Endocr Pathol 23 21-33 2012.

  • Ohta S Lai EW Pang AL Bro uwers FM Chan WY Eisenhofer G de Krijger R Ksinantova L Breza J Blazicek P Kvetnansky R Wesley RA Pacak K. Downregulation of metastasis suppressor genes in malignant pheochromocytoma. Int J Cancer 114 139-143 2005.

  • Oishi T Iino K Okawa Y Ka kizawa K Matsunari S Yamashita M Taniguchi T Maekawa M Suda T Oki Y. DNA methylation analysis in malignant pheochromocytoma and paraganglioma. J Clin Transl Endocrinol 7 12- 20 2016

  • Palmada M Kanwal S Rutkosk i NJ Gustafson-Brown C Johnson RS Wisdom R Carter BD. c-jun is essential for sympathetic neuronal death induced by NGF withdrawal but not by p75 activation. J Cell Biol 158 453-461 2002.

  • Peczkowska M Cwikla J Kidd M Lewczuk A Kolasinska-Cwikla A Niec D Michalowska I Prejbisz A Januszewicz A Chiarelli J Bodei L Modlin I. Th e clinical utility of circulating neuroendocrine gene transcript analysis in well-diff erentiated paragangliomas and pheochromocytomas. Eur J Endocrinol 176 143-157 2017.

  • Pavel M Jann H Prasad V Drozdov I Modlin IM Kidd M. NET blood transcript analysis defi nes the crossing of the clinical rubicon: When stable disease becomes progressive. Neuroendocrinology 104 170-182 2017.

  • Perrino CM Ho A Dall CP Z ynger DL. Utility of GATA3 in the diff erential diagnosis of pheochromocytoma. Histopathology 71 475-479 2017.

  • Pillai S Gopalan V Smith R A Lam AK. Updates on the genetics and the clinical impacts on phaeochromocytoma and paraganglioma in the new era. Crit Rev Oncol Hematol 100 190-208 2016.

  • Rao D Peitzsch M Prejbisz A Hanus K Fassnacht M Beuschlein F Brugger C Fliedner S Langton K Pamporaki C Gudziol V Stell A Januszewicz A Timmers HJLM Lenders JWM Eisenhofer G. Plasma methoxytyramine: clinical utility with metanephrines for diagnosis of pheochromocytoma and paraganglioma. Eur J Endocrinol 177 103-113 2017.

  • Saffar H Sanii S Heshmat R Haghpanah V Larijani B Rajabiani A Azimi S Tavangar SM. Expression of galectin-3 nm-23 and cyclooxygenase-2 could potentially discriminate between benign and malignant pheochromocytoma. Am J Clin Pathol 135 454-460 2011.

  • Salajegheh A Smith RA Kase m K Gopalan V Nassiri MR William R Lam AK. Single nucleotide polymorphisms and mRNA expression of VEGF-A in papillary thyroid carcinoma: potential markers for aggressive phenotypes. Eur J Surg Oncol 37 93-99 2011.

  • Salajegheh A Pakneshan S Rahman A Dolan-Evans E Zhang S Kwong E Gopalan V Lo CY Smith RA Lam AK. Co-regulatory potential of vascular endothelial growth factor-A and vascular endothelial growth factor-C in thyroid carcinoma. Hum Pathol 44 2204-2212 2013.

  • Salmenkivi K Haglund C Ris timaki A Arola J Heikkila P. Increased expression of cyclooxygenase-2 in malignant pheochromocytomas. J Clin Endocrinol Metab 86 5615-5619 2001.

  • Salmenkivi K Heikkila P Li u J Haglund C Arola J. VEGF in 105 pheochromocytomas: enhanced expression correlates with malignant outcome. AMPIS 111 458-464 2003.

  • Salmenkivi K Heikkila P Haglund C Arola J. Malignancy in pheochromocytomas. AMPIS 112 551-559 2004.

  • Sandgren J Andersson R Rad a-Iglesias A Enroth S Akerstrom G Dumanski JP Komorowski J Westin G Wadelius C. Integrative epigenomic and genomic analysis of malignant pheochromocytoma. Exp Mol Med 42 484-502 2010.

  • Sanii S Saffar H Tabriz HM Qorbani M Haghpanah V Tavangar SM. Expression of matrix metalloproteinase-2 but not caspase-3 facilitates distinction between benign and malignant thyroid follicular neoplasms. Asian Pac J Cancer Prev 13 2175-2178 2012.

  • Sarmadi S Izadi-Mood N Sot oudeh K Tavangar SM. Altered PTEN expression; a diagnostic marker for diff erentiating normal hyperplastic and neoplastic endometrium. Diagn Pathol 4 41 2009.

  • Scholz T Schulz C Klose S Lehnert H. Diagnostic management of benign and malignant pheochromocytoma. Exp Clin Endocrinol Diabetes 115 155-159 2007.

  • Shuch B Ricketts CJ Metwal li AR Pacak K Linehan WM. Th e genetic basis of pheochromocytoma and paraganglioma: implications for management. Urology 83 1225-1232 2014.

  • Stenstrom G Svardsudd K. Ph eochromocytoma in Sweden 1958-1981. An analysis of the National Cancer Registry Data. Acta Med Scand 220 225-232 1986.

  • Strong VE Kennedy T Al-Ahm adie H Tang L Coleman J Fong Y Brennan M Ghossein RA. Prognostic indicators of malignancy in adrenal pheochromocytomas: clinical histopathologic and cell cycle/apoptosis gene expression analysis. Surgery 143 759-768 2008.

  • Tabriz HM Adabi Kh Lashkar i A Heshmat R Haghpanah V Larijani B Tavangar SM. Immunohistochemical analysis of nm23 protein expression in thyroid papillary carcinoma and follicular neoplasm. Pathol Res Pract 205 83-87 2009.

  • Tavangar SM Larijani B Mah ta A Hosseini SM Mehrazine M Bandarian F. Craniopharyngioma: a clinicopathological study of 141 cases. Endocr Pathol 15 339-344 2004.

  • Tavangar SM Sharift abrizi A Soroush AR. Her-2/neu over-expression correlates with more advanced disease in Iranian colorectal cancer patients. Med Sci Monit 11 CR123-CR126 2005.

  • Tavangar SM Monajemzadeh M Larijani B Haghpanah V. Immunohistochemical study of oestrogen receptors in 351 human thyroid glands. Singapore Med J 48 744-747 2007.

  • Tavangar SM Shojaee A Moradi Tabriz H Haghpanah V Larijani B Heshmat R Lashkari A Azimi S. Immunohistochemical expression of Ki67 c-erbB-2 and c-kit antigens in benign and malignant pheochromocytoma. Pathol Res Pract 206 305-309 2010.

  • Thompson LD. Pheochromocytom a 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 26 551-566 2002.

  • Thouennon E Elkahloun AG G uillemot J Gimenez-Roqueplo AP Bertherat J Pierre A Ghzili H Grumolato L Muresan M Klein M Lefebvre H Ouafi k L Vaudry H Plouin PF Yon L Anouar Y. Identifi cation of potential gene markers and insights into the pathophysiology of pheochromocytoma malignancy. J Clin Endocrinol Metab 92 4865-4872 2007.

  • van der Harst E Bruining HA Jaap Bonjer H van der Ham F Dinjens WN Lamberts SW de Herder WW Koper JW Stijnen T Proye C Lecomte-Houcke M Bosman FT de Krijger RR. Proliferative index in phaeochromocytomas: does it predict the occurrence of metastases? J Pathol 191 175-180 2000.

  • Vaque JP Fernandez-Garcia B Garcia-Sanz P Ferrandiz N Bretones G Calvo F Crespo P Marin MC Leon J. c-Myc inhibits Ras-mediated diff erentiation of pheochromocytoma cells by blocking c-Jun up-regulation. Mol Cancer Res 6 325-339 2008.

  • Vogel KS Brannan CI Jenkin s NA Copeland NG Parada LF. Loss of neurofi bromin results in neurotrophin-independent survival of embryonic sensory and sympathetic neurons. Cell 82 733-742 1995.

  • Welander J Andreasson A Br auckhoff M Backdahl M Larsson C Gimm O Soderkvist P. Frequent EPAS1/HIF2α exons 9 and 12 mutations in non-familial pheochromocytoma. Endocr Relat Cancer 21 495-504 2014.

  • Walenkamp A Crespo G Fierro Maya F Fossmark R Igaz P Rinke A Tamagno G Vitale G Oberg K Meyer T. Hallmarks of gastrointestinal neuroendocrine tumours: implications for treatment. Endocr Relat Cancer 21 R445-R460 2014.

  • Wilzen A Rehammar A Muth A N ilsson O Tesan Tomic T Wangberg B Kristiansson E Abel F. Malignant pheochromocytomas/paragangliomas harbor mutations in transport and cell adhesion genes. Int J Cancer 138 2201-2211 2016.

  • Yalcin S Oberg K (Eds). Neuroe ndocrine Tumours. Diagnosis and Management. Springer-Verlag Berlin Heidelberg 2015.

  • Yang C Zhuang Z Fliedner SM Shankavaram U Sun MG Bullova P Zhu R Elkahloun AG Kourlas PJ Merino M Kebebew E Pacak K. Germ-line PHD1 and PHD2 mutations detected in patients with pheochromocytoma/paraganglioma-polycythemia. J Mol Med (Berl) 93 93-104 2015.

  • Yon L Guillemot J Montero-Hadjadje M Grumolato L Leprince J Lefebvre H Contesse V Plouin PF Vaudry H Anouar Y. Identifi cation of the secretogranin II-derived peptide EM66 in pheochromocytomas as a potential marker for discriminating benign versus malignant tumors. J Clin Endocrinol Metab 88 2579-2585 2003.

  • Yu R Nissen NN Chopra P Dhall D Phillips E Wei M. Diagnosis and treatment of pheochromocytoma in an acade mic hospital from 1997 to 2007. Am J Med 122 85-95 2009.

  • Yuan W Wang W Cui B Su T Ge Y Jiang L Zhou W Ning G. Overexpression of ERBB-2 was more frequently detec ted in malignant than benign pheochromocytomas by multiplex ligation-dependent probe amplifi cation and immunohistochemistry. Endocr Relat Cancer 15 343-350 2008.

  • Zhikrivetskaya SO Snezhkina AV Zaretsky AR Alekseev BY Pokrovsky AV Golovyuk AL Melnikova NV Stepanov O A Kalinin DV Moskalev AA Krasnov GS Dmitriev AA Kudryavtseva AV. Molecular markers of paragangliomas/pheochromocytomas. Oncotarget 8 25756-25782 2017.

Search
Journal information
Impact Factor


CiteScore 2018: 1.27

SCImago Journal Rank (SJR) 2018: 0.411
Source Normalized Impact per Paper (SNIP) 2018: 0.441

Cited By
Metrics
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 757 499 30
PDF Downloads 534 364 10