Department of Endocrinology, Metabolism, and Cancer, Institut National de la Santé et de la Recherche Médicale Unité 1016, Paris, France.
J Clin Endocrinol Metab. 2011 Feb;96(2):E419-26. doi: 10.1210/jc.2010-1885. Epub 2010 Nov 17.
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.
The objective of the study was to describe the Wnt/β-catenin pathway alterations in 100 ACAs and their association with clinicopathological characteristics.
One hundred consecutive ACAs (excluding Conn's adenomas) were studied clinically by β-catenin immunohistochemistry and direct sequencing of CTNNB1.
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).
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.
已有研究报道，β-连环蛋白（β-catenin）免疫组化异常和β-连环蛋白基因（CTNNB1）突变存在于肾上腺皮质腺瘤（ACAs）中，但这些缺陷的频率及其肿瘤表型尚未明确。
本研究旨在描述 100 例 ACAs 中 Wnt/β-catenin 通路的改变，并探讨其与临床病理特征的关系。
连续对 100 例（不包括 Conn 腺瘤）ACAs 进行β-catenin 免疫组化和 CTNNB1 直接测序。
35 例为无功能腺瘤（NSAs），19 例为亚临床分泌皮质醇的腺瘤（SCSAs），46 例为分泌皮质醇的腺瘤（CSAs）。51 例肿瘤的细胞质和/或核β-catenin 免疫组化染色异常，表明存在 Wnt/β-catenin 通路改变。36 例肿瘤存在 CTNNB1 突变，均伴有异常的免疫组化β-catenin 聚集。在 64 例无突变的肿瘤中，仅有 15 例（23%）显示细胞质和/或核β-catenin 染色（P<0.0001）。携带 CTNNB1 突变的肿瘤主要为无功能（61% NSA，22% SCSA，16% CSA），而非突变肿瘤主要为有功能（20% NSA，17% SCSA，62% CSA）（P<0.0001）。携带 CTNNB1 突变的肿瘤平均直径和重量分别为 4.2cm（±1.3）和 28.4g（±21.4），而非突变肿瘤分别为 3.4cm（±0.9）和 18.2g（±8.2）（P<0.01）。
ACAs 中约有一半存在细胞质和/或核β-catenin 免疫组化染色异常，提示 Wnt/β-catenin 通路的激活，这可能与 70%病例中 CTNNB1 的激活突变有关。CTNNB1 突变主要发生于较大的无功能肿瘤中，提示 Wnt/β-catenin 通路的激活与分化程度较低的 ACAs 的发生有关。
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