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P Soon, Cancer Genetics, Kolling Institute of Medical Research, University of Sydney, St Leonards, 2065, Australia
A Gill, Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, Australia
D Benn, Cancer Genetics, Kolling Institute of Medical Research, University of Sydney, St Leonards, Australia
A Clarkson, Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, Australia
B Robinson, Cancer Genetics, Kolling Institute of Medical Research, University of Sydney, St Leonards, Australia
K McDonald, Cancer Genetics, Kolling Institute of Medical Research, University of Sydney, St Leonards, Australia
S Sidhu, 7 Department of Endocrine and Oncology Surgery, Royal North Shore Hospital, Paris, France

Correspondence: Patsy Soon, Email: patsysoon{at}med.usyd.edu.au

Abstract

The management of adrenocortical tumours (ACTs) is complex. The Weiss score is the current most widely used system for ACT diagnosis. An ACT is scored from 0 to 9, with a higher score correlating with increased malignancy. However, ACTs with a score of 3 can be phenotypically benign or malignant. Our objective is to use microarray profiling of a cohort of adrenocortical carcinomas (ACCs) and adrenocortical adenomas (ACAs) to identify discriminatory genes that could be used as an adjunct to the Weiss score. A cohort of Weiss score defined ACCs and ACAs were profiled using Affymetrix HGU133plus2.0 genechips. Genes with high discriminatory power were identified by univariate and multivariate analyses and confirmed by quantitative PCR (qPCR) and immunohistochemisty (IHC). The expression of IGF2, MAD2L1, and CCNB1 were significantly higher in ACCs compared to ACAs while ABLIM1, NAV3, SEPT4 and RPRM were significantly lower. Several proteins, including IGF2, MAD2L1, CCNB1 and Ki-67 had high diagnostic accuracy in differentiating ACCs from ACAs. The best results however were obtained with a combination of IGF2 and Ki-67, with 96% sensitivity and 100% specificity in diagnosing ACCs. Microarray gene expression profiling accurately differentiates ACCs from ACAs. The combination of IGF2 and Ki-67 IHC is also highly accurate in distinguishing between the 2 groups and is particularly helpful in ACTs with Weiss score of 3.

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				L. J. Tacon, P. S. Soon, A. J. Gill, A. S. Chou, A. Clarkson, J. Botling, P. L. H. Stalberg, B. M. Skogseid, B. G. Robinson, S. B. Sidhu, et al. The Glucocorticoid Receptor Is Overexpressed in Malignant Adrenocortical Tumors J. Clin. Endocrinol. Metab., November 1, 2009; 94(11): 4591 - 4599. [Abstract] [Full Text] [PDF]