Wnt/β-catenin pathway activation in adrenocortical adenomas is frequently due to somatic CTNNB1-activating mutations, which are associated with larger and nonsecreting tumors: a study in cortisol-secreting and -nonsecreting tumors
Abstract
BACKGROUND: Abnormal β-catenin immunohistochemistry and mutations of the β-catenin gene (CTNNB1) have been reported in adrenocortical adenomas (ACAs), but the frequencies of these defects and the phenotype of such tumors have not been clearly determined. OBJECTIVE: The objective of the study was to describe the Wnt/β-catenin pathway alterations in 100 ACAs and their association with clinicopathological characteristics. PATIENTS AND METHODS: One hundred consecutive ACAs (excluding Conn's adenomas) were studied clinically by β-catenin immunohistochemistry and direct sequencing of CTNNB1. RESULTS: Thirty-five ACAs were nonsecreting adenomas (NSAs), 19 were subclinical cortisol secreting adenomas (SCSAs), and 46 were cortisol secreting adenomas (CSAs). Fifty-one tumors had abnormal cytoplasmic and/or nuclear β-catenin immunohistochemical staining, indicating Wnt/β-catenin pathway alteration. Thirty-six tumors showed CTNNB1 mutations, which all showed abnormal immunohistochemical β-catenin accumulation. Among the 64 nonmutated tumors, only 15 (23%) showed cytoplasmic and/or nuclear β-catenin staining (P < 0.0001). Tumors with CTNNB1 mutations were predominantly nonsecreting (61% NSAs, 22% SCSAs, 16% CSAs) whereas nonmutated tumors were predominantly secreting (20% NSAs, 17% SCSAs, 62% CSAs) (P < 0.0001). Mean tumor size and weight were, respectively, 4.2 cm (± 1.3) and 28.4 g (± 21.4) for tumors with CTNNB1 mutations vs. 3.4 cm (± 0.9) and 18.2 g (± 8.2) for nonmutated tumors (P < 0.01). CONCLUSIONS: Abnormal cytoplasmic and/or nuclear β-catenin immunohistochemical staining occurs in about half of ACAs. This suggests the activation of the Wnt/β-catenin pathway, which could be explained by activating mutations of CTNNB1 in 70% of the cases. CTNNB1 mutations are mainly observed in larger and nonsecreting ACAs, suggesting that the Wnt/β-catenin pathway activation is associated with the development of less differentiated ACAs.
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In one study of 100 surgically excised adrenal adenomas, 36% contained CTNNB1 mutations.
“In 1 study of 100 adrenal adenomas that had been surgically excised, 36% were found to contain CTNNB1 mutations (141).”
From Adrenal incidentaloma (2020) · cites this paper as [141]
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- Authors
- Bonnet, S., Gaujoux, S., Launay, P., Baudry, C., Chokri, I., Ragazzon, B., Libé, R., René-Corail, F., Audebourg, A., Vacher-Lavenu, M.-C., Groussin, L., Bertagna, X., Dousset, B., Bertherat, J., & Tissier, F.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Hôpital Cochin (FR)
- Corresponding author
- Tissier, Frédérique
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2011-02
- Volume
- 96
- Issue
- 2
- Pages
- E419-E426
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2103452905
- Cited by
- 133
- References
- 39
- Citations by year
- 2026: 12 · 2025: 3 · 2024: 6 · 2023: 2 · 2022: 9 · 2021: 10 · 2020: 8 · 2019: 5 · 2018: 9 · 2017: 15 · 2016: 10 · 2015: 10 · 2014: 9 · 2013: 7 · 2012: 8
- FWCI
- 8.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- adrenal adenoma, Wnt/β-catenin signaling, CTNNB1 mutation, β-catenin immunohistochemistry, tumor size, tumor weight, clinicopathological correlation, adrenocortical carcinoma, Cushing's disease, adrenocortical hyperplasia
- MeSH terms
- Adenoma, Adrenal Cortex Neoplasms, Adult, DNA Mutational Analysis, DNA, Neoplasm, Female, Humans, Hydrocortisone, Immunohistochemistry, Male, Middle Aged, Mutation, Phenotype, RNA, Neoplasm, Signal Transduction, Wnt Proteins, beta Catenin
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