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. 2014 Mar;64(4):567-76.
doi: 10.1111/his.12283. Epub 2013 Nov 23.

Distinguishing adrenal cortical carcinomas and adenomas: a study of clinicopathological features and biomarkers

Cuiping Wang  1 , Yang Sun, Huanwen Wu, Dachun Zhao, Jie Chen
Affiliations
Free PMC article

Distinguishing adrenal cortical carcinomas and adenomas: a study of clinicopathological features and biomarkers

Cuiping Wang et al. Histopathology. 2014 Mar.
Free PMC article

Abstract

Aims: To determine clinicopathological criteria and molecular markers helpful in distinguishing adrenocortical carcinomas (ACCs) from adrenocortical adenomas (ACAs).

Methods and results: We analysed retrospectively the clinical and pathological features of 50 adrenal cortical tumours, and tested the expression of miR483-3p by in-situ hybridization as well as the expression of IGF2 and Smad4 by immunohistochemistry. We found that tumour size, tumour weight, hormonal function and the Weiss system are all high-efficacy criteria for differentiating malignant from benign tumours (P < 0.001). MiR483-3p was overexpressed in 68% (17 of 25) of ACCs compared to 12% (three of 25) of ACAs (P < 0.05). Using a combination of miR483-3p and Smad4 improved diagnostic accuracy. Molecular markers were then tested in an independent set of 15 borderline tumours. We confirmed that the combined use of miR483-3p and Smad4 immunochemistry can complement the Weiss score in the diagnosis of ACC in cases that display borderline histology.

Conclusions: Tumour size, tumour weight, hormonal function and the Weiss system are useful clinicopathological criteria that can result in accurate diagnosis of most ACCs and ACAs. In challenging cases, miR483-3p and Smad4 expression may help in distinguishing these two entities.

Keywords: adrenal cortical tumours; clinicopathological features; diagnosis; differentiation; hsa-mir-483-3p; in-situ hybridization.

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Figures

Figure 1
Figure 1
Representative staining for miR483-3p, IGF2 and Smad4 in adrenal cortical tumours. MiR483-3p was detected by in-situ hybridization (ISH), and IGF2 and Smad4 by immunochemistry. A, MiR483-3p in an adrenocortical carcinoma (ACC). The miR483-3p ISH signal is expressed mainly in the cytoplasm in all tumour cells of the ACC. Positive staining has a blue–violet colour. B, Perinuclear dot-like and homogeneous cytoplasmic staining for IGF2 in all or nearly all tumour cells in the same ACC correlating with the expression of miR483-3p (4+ staining). C, Smad4 in an ACC showing negative staining (score 0). Note positive labelling in the non-neoplastic fibrous tissue on the left. D, Negative miR483-3p ISH in an ACA. E, IGF2 in an ACA showing 1+ staining. Note intra-cytoplasmic specks only. F, An ACA displaying strong, diffuse cytoplasmic and occasional nuclear expression of Smad4.
Figure 2
Figure 2
Kaplan–Meier analyses of patients with elevated miR483-3p and negative/low Smad4 expression, compared to other patients.
See this image and copyright information in PMC

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