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Published on: September 15, 2017
The prevalence of CTNNB1 mutations in primary aldosteronism and consequences for clinical outcomes
Vin-Cent Wu1, Shuo-Meng Wang2, Shih-Chieh Jeff Chueh3
1Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Abstract:
Constitutive activation of the Wnt pathway/β-catenin signaling may be important in aldosterone-producing adenoma (APA). However, significant gaps remain in our understanding of the prevalence and clinical outcomes after adrenalectomy in APA patients harboring CTNNB1 mutations. The molecular expression of CYP11B2 and gonadal receptors in adenomas were also explored. Adenomas from 219 APA patients (95 men; 44.2%; aged 50.5 ± 11.9 years) showed a high rate of somatic mutations (n = 128, 58.4%). The majority of them harbored KCNJ5 mutations (n = 116, 52.9%); 8 patients (3.7%, 6 women) had CTNNB1 mutations. Patients with APAs harboring CTNNB1 mutations were older and had shorter duration of hypertension. After adrenalectomy, CTNNB1 mutation carriers had a higher possibility (87.5%) of residual hypertension than other APA patients. APAs harboring CTNNB1 mutations have heterogeneous staining of β-catenin and variable expression of gonadal receptors and both CYP11B1 and CYP11B2. This suggests that CTNNB1 mutations may be more related to tumorigenesis rather than excessive aldosterone production.
Insights
Aldosterone-producing adenoma (APA) patients with CTNNB1 mutations show higher rates of persistent hypertension post-adrenalectomy. These mutations may drive tumor development rather than excess aldosterone production.
Area of Science:
- Endocrinology
- Oncology
- Genetics
Background:
- Constitutive Wnt pathway/β-catenin signaling is implicated in aldosterone-producing adenomas (APAs).
- Limited understanding exists regarding CTNNB1 mutations' prevalence and clinical impact in APA patients.
Purpose of the Study:
- To investigate the prevalence and clinical outcomes of CTNNB1 mutations in APA patients.
- To explore molecular expression of CYP11B2 and gonadal receptors in relation to CTNNB1 mutations.
Main Methods:
- Somatic mutation analysis in adenomas from 219 APA patients.
- Clinical data review including age, hypertension duration, and post-adrenalectomy outcomes.
- Immunohistochemical analysis of β-catenin, gonadal receptors, CYP11B1, and CYP11B2 expression.
Main Results:
- Somatic mutations were found in 58.4% of APAs; KCNJ5 mutations were most common (52.9%).
- CTNNB1 mutations were identified in 3.7% of patients (8 individuals).
- CTNNB1 mutation carriers were older, had shorter hypertension duration, and higher rates of residual hypertension (87.5%) after adrenalectomy.
Conclusions:
- CTNNB1 mutations in APAs are associated with increased risk of persistent hypertension post-surgery.
- Heterogeneous β-catenin staining and variable receptor expression in CTNNB1-mutated APAs suggest a role in tumorigenesis over aldosterone excess.
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