title: Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas.
abstract: BACKGROUND
  Pheochromocytomas and paragangliomas may be malignant either at presentation or during recurrence, but the clinical course of malignant tumors is unpredictable.
  
  
  OBJECTIVE
  The objective was to analyze survival according to clinical characteristics at diagnosis of malignancy and the presence or absence of SDHB mutations.
  
  
  METHODS
  This was a retrospective cohort study.
  
  
  METHODS
  A total of 54 patients with malignant tumors were included. Malignancy was scored according to the presence of metastases or histologically documented lymph node invasion.
  
  
  METHODS
  The main outcome was the specific survival after the diagnosis of the first metastasis.
  
  
  RESULTS
  Germline mutations were identified in SDHB (n = 23, including 21 patients with apparent sporadic tumors) and VHL (n = 1) genes, and two patients had neurofibromatosis 1. Patients were followed up from the diagnosis of primary tumor and from the diagnosis of the first metastasis to the present or to death with medians of 79 [interquartile range (IQR) 24; 190] and 39 [IQR 14; 94] months, respectively. The 5-yr probability of survival after the diagnosis of the first metastasis was 0.55 (95% confidence interval 0.39-0.69). Patients with SDHB mutations were younger, more frequently had extra-adrenal tumors, and had a shorter metanephrine excretion doubling time. The presence of SDHB mutations was significantly and independently associated with mortality (relative risk 2.7; 95% confidence interval 1.2, 6.4; P = 0.021).
  
  
  CONCLUSIONS
  SDHB mutations, frequent in patients with malignant pheochromocytomas or paragangliomas, are associated with shorter survival. Therefore, SDHB genetic testing may be of prognostic value for such patients, even those with an apparent sporadic and/or benign presentation at diagnosis.
authors.affiliation: Hypertension Unit, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75908 Paris cedex 15, France. laurence.amar@egp.aphp.fr
authors.forename: Laurence
authors.initials: L
authors.lastname: Amar
authors.forename: Eric
authors.initials: E
authors.lastname: Baudin
authors.forename: Nelly
authors.initials: N
authors.lastname: Burnichon
authors.forename: Séverine
authors.initials: S
authors.lastname: Peyrard
authors.forename: Stéphane
authors.initials: S
authors.lastname: Silvera
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bertherat
authors.forename: Xavier
authors.initials: X
authors.lastname: Bertagna
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaitre
authors.forename: Anne-Paule
authors.initials: AP
authors.lastname: Gimenez-Roqueplo
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Plouin
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D018095:Germ-Line Mutation; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010235:Paraganglioma / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D010673:Pheochromocytoma / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase / Q000235:genetics*; D015996:Survival Rate
chemical_list: D007506:Iron-Sulfur Proteins; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase