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

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.