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

被引：100

作者：

Bonnet, Stephane ^{[3
,5
,6
]}

Gaujoux, Sebastien ^{[3
,5
,6
]}

Launay, Pierre ^{[6
]}

Baudry, Camille ^{[5
,6
]}

Chokri, Ilham

Ragazzon, Bruno ^{[5
,6
]}

Libe, Rossella ^{[2
,4
,5
,6
]}

Rene-Corail, Fernande ^{[6
]}

Audebourg, Anne

Vacher-Lavenu, Marie-Cecile ^{[5
]}

Groussin, Lionel ^{[2
,4
,5
,6
]}

Bertagna, Xavier ^{[2
,4
,5
,6
]}

Dousset, Bertrand ^{[2
,3
,5
,6
]}

Bertherat, Jerome ^{[2
,4
,5
,6
]}

Tissier, Frederique ^{[1
,2
,5
,6
]}

机构：

[1] Hop Cochin, AP HP, Dept Pathol, Serv Anat & Cytol Pathol, F-75014 Paris, France

[2] COMETE INCA Rare Adrenal Canc Network, F-75014 Paris, France

[3] Hop Cochin, AP HP, Dept Digest & Endocrine Surg, F-75014 Paris, France

[4] Hop Cochin, AP HP, Dept Endocrinol, Ctr Rare Adrenal Dis, F-75014 Paris, France

[5] Univ Paris 05, F-75014 Paris, France

[6] Inst Cochin Genet Mol, Dept Endocrinol Metab & Canc, Inst Natl Sante & Rech Med, Ctr Natl Rech Sci,Unite Mixte Rech 8104,U1016, F-75014 Paris, France

来源：

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2011年 / 96卷 / 02期

关键词：

BETA-CATENIN; HEPATOCELLULAR ADENOMA; COLORECTAL CARCINOMAS; DISEASE PPNAD; COLON-CANCER; GENE; APC; EXPRESSION; PATHOPHYSIOLOGY; CLASSIFICATION;

D O I：

10.1210/jc.2010-1885

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Abnormal beta-catenin immunohistochemistry and mutations of the beta-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/beta-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 beta-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 beta-catenin immunohistochemical staining, indicating Wnt/beta-catenin pathway alteration. Thirty-six tumors showed CTNNB1 mutations, which all showed abnormal immunohistochemical beta-catenin accumulation. Among the 64 nonmutated tumors, only 15 (23%) showed cytoplasmic and/or nuclear beta-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 beta-catenin immunohistochemical staining occurs in about half of ACAs. This suggests the activation of the Wnt/beta-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/beta-catenin pathway activation is associated with the development of less differentiated ACAs. (J Clin Endocrinol Metab 96: E419-E426, 2011)

引用

页码：E419 / E426

页数：8

共 38 条

[1] Cholestasis is a marker for hepatocellular carcinomas displaying β-catenin mutations [J].