CTNNB1 mutations in adrenocortical adenomas were significantly associated with nonsecreting status (61% vs 20% in nonmutated tumors, P<0.0001) and larger mean tumor size (4.2 cm vs 3.4 cm, P<0.01).
Observational (n=100)
CTNNB1 mutations occur in about a third of adrenocortical adenomas and are associated with larger, nonsecreting tumors, suggesting a role in the development of less differentiated adenomas.
Absolute Event Rate: 61% vs 20%
p-value: p=<0.0001
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.
Bonnet et al. (Wed,) conducted a observational in Adrenocortical Adenomas (n=100). CTNNB1 mutations vs. Nonmutated tumors was evaluated on Nonsecreting tumor phenotype (p=<0.0001). CTNNB1 mutations in adrenocortical adenomas were significantly associated with nonsecreting status (61% vs 20% in nonmutated tumors, P<0.0001) and larger mean tumor size (4.2 cm vs 3.4 cm, P<0.01).