Journal
CLINICAL CANCER RESEARCH
Volume 17, Issue 2, Pages 328-336Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-10-2006
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Funding
- Contrat d'Initiation a la Recherche Clinique [CIRC 05045 - AP-HP]
- Recherche Translationnelle DHOS/INCA [RTD09024]
- German Ministry of Research BMBF [01KG0501]
- German Research Foundation DFG [FA 466/3-1]
- Fonds d'Etude et de Recherche du Corps Medical (FERCM) - AP-HP - Paris
- Association Benoit Malassagne - Paris, France
- Conny-Maeva foundation
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Purpose: Activation of the Wnt/beta-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 beta-catenin immunohistochemistry and CTNNB1 (beta-catenin gene)/APC (adenomatous polyposis coli gene) mutations in patients with resected primary ACC. Experimental design: In 79 patients with resected primary ACC from a French cohort (Cochin-COMETE), beta-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 beta-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. beta-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/beta-catenin activation, confirmed by the presence of beta-catenin nuclear staining, is an independent prognostic factor of overall and disease-free survival in patients with resected primary ACC. Clin Cancer Res; 17(2); 328-36. (C)2010 AACR.
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