title: β-catenin activation is associated with specific clinical and pathologic characteristics and a poor outcome in adrenocortical carcinoma.
abstract: OBJECTIVE
  Activation of the Wnt/β-catenin signaling pathway is frequent in adrenocortical carcinoma (ACC) and might be associated with a more aggressive phenotype. The objective of this study was to assess the prognostic value of β-catenin immunohistochemistry and CTNNB1 (β-catenin gene)/APC (adenomatous polyposis coli gene) mutations in patients with resected primary ACC.
  
  
  METHODS
  In 79 patients with resected primary ACC from a French cohort (Cochin-COMETE), β-catenin expression was assessed on tumor specimens by immunohistochemistry. For patients with available DNA (n = 49), CTNNB1, and APC hotspot (mutation cluster region), were sequenced. Association between these results and the clinicopathologic characteristics of the ACC and overall and disease-free survival were studied. Results were confirmed on a tissue microarray from an independent multicentric cohort of 92 ACC from Germany (German-ENSAT cohort).
  
  
  RESULTS
  In the Cochin-COMETE cohort, the presence of a β-catenin nuclear staining was significantly associated with a higher ENSAT tumor stage (i.e., stages III and IV), higher Weiss score, more frequent necrosis, mitoses, and CTNNB1/APC mutations. β-Catenin nuclear staining and the presence of CTNNB1/APC mutations were both associated with decreased overall and disease-free survival, and were independent predictive factors of survival in multivariate analysis. The same results were observed in the German-ENSAT cohort.
  
  
  CONCLUSIONS
  Wnt/β-catenin activation, confirmed by the presence of β-catenin nuclear staining, is an independent prognostic factor of overall and disease-free survival in patients with resected primary ACC.
authors.affiliation: Cochin Institute, Paris Descartes University, CNRS (UMR 8104), Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gaujoux
authors.forename: Sophie
authors.initials: S
authors.lastname: Grabar
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
authors.forename: Bruno
authors.initials: B
authors.lastname: Ragazzon
authors.forename: Pierre
authors.initials: P
authors.lastname: Launay
authors.forename: Rossella
authors.initials: R
authors.lastname: Libé
authors.forename: Ilham
authors.initials: I
authors.lastname: Chokri
authors.forename: Anne
authors.initials: A
authors.lastname: Audebourg
authors.forename: Benedict
authors.initials: B
authors.lastname: Royer
authors.forename: Silviu
authors.initials: S
authors.lastname: Sbiera
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Vacher-Lavenu
authors.forename: Bertrand
authors.initials: B
authors.lastname: Dousset
authors.forename: Xavier
authors.initials: X
authors.lastname: Bertagna
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bertherat
authors.forename: Frédérique
authors.initials: F
authors.lastname: Tissier
mesh_terms: D018268:Adrenocortical Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D018572:Disease-Free Survival; D005260:Female; D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016896:Treatment Outcome; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin