β-Catenin activation is associated with specific clinical and pathologic characteristics and a poor outcome in adrenocortical carcinoma
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Abstract
PURPOSE: 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. EXPERIMENTAL DESIGN: 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.
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Mutations in CTNNB1 are present in adrenocortical carcinomas and may be associated with poor outcome.
“As previously described, mutations in CTNNB1 are also present in ACCs and may be associated with poor outcome (164).”
From Adrenal incidentaloma (2020) · cites this paper as [164]
High-grade ACCs are enriched for mutations of TP53 and/or CTNNB1, and these mutations tend to be mutually exclusive.
“High-grade ACCs are enriched for mutations of TP53 (14, 140–142) and/or CTNNB1 (143–149), and these mutations tend to be mutually exclusive (reviewed in Ref. 150).”
From Adrenocortical carcinoma (2014) · cites this paper as [146]
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References 46 · Cited by 146
- Authors
- Gaujoux, S., Grabar, S., Fassnacht, M., Ragazzon, B., Launay, P., Libé, R., Chokri, I., Audebourg, A., Royer, B., Sbiera, S., Vacher-Lavenu, M.-C., Dousset, B., Bertagna, X., Allolio, B., Bertherat, J., & Tissier, F.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Authors' Affiliations: 1Cochin Institute, Paris Descartes University, CNRS (UMR 8104), 2Inserm, U1016, 3AP-HP, Cochin Hospital, Department of Digestive and Endocrine Surgery, 4AP-HP, Cochin Hospital, Unit of Biostatistic and Epidemiology, 5Paris Descartes University, Paris, France; 6University of Wuerzburg, University Hospital, Department of Internal Medicine I, Endocrine and Diabetes Unit, 97080 Wuerzburg, Germany; 7Rare Adrenal Cancer Network-Corticomédullosurrénale Tumeur Endocrine, Institut National du Cancer, 8AP-HP, Cochin Hospital, Department of Endocrinology, Center for Rare Adrenal Diseases, and 9AP-HP, Cochin Hospital, Department of Pathology, Paris, France
- Corresponding author
- Tissier, Frédérique
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2011-01-15
- Volume
- 17
- Issue
- 2
- Pages
- 328-336
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2146718910
- Cited by
- 146
- References
- 46
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 2 · 2023: 7 · 2022: 6 · 2021: 6 · 2020: 11 · 2019: 11 · 2018: 10 · 2017: 11 · 2016: 10 · 2015: 14 · 2014: 9 · 2013: 13 · 2012: 13
- FWCI
- 11.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Université Paris Descartes
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Keywords
- adrenocortical carcinoma, β-catenin, Wnt/β-catenin signaling, CTNNB1 mutation, APC mutation, prognostic factors, overall survival, disease-free survival, tumor stage, Weiss score, tumor necrosis
- MeSH terms
- Adult, Female, Humans, Immunohistochemistry, Male, Middle Aged, Mutation, Treatment Outcome, Genes, APC, Adrenocortical Carcinoma, Disease-Free Survival, beta Catenin
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