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Gustavo G. Fernandez-Ranvier, MD; Julie Weng, BS; Ru-Fang Yeh, PhD; Elham Khanafshar, MD; Insoo Suh, MD; Christopher Barker, PhD; Quan Yang Duh, MD; Orlo H. Clark, MD; Electron Kebebew, MD

Arch Surg. 2008;143(9):841-846.

Hypothesis  The gene expression profiles of benign and malignant adrenocortical tumors are different.

Design  Genomewide gene expression profiling and validation.

Setting  Tertiary medical center.

Patients  Eighty-five patients with benign adrenocortical tumors (n = 74) and adrenocortical carcinoma (n = 11).

Intervention  Real-time quantitative reverse transcription–polymerase chain reaction (RT-PCR) in 89 adrenocortical tissue samples (11 malignant and 78 benign). The criteria for differentially expressed genes between benign and malignant adrenocortical tumors were a false discovery rate of less than 5% and an adjusted P < .01. Genes differentially expressed by 8-fold higher or lower were validated by RT-PCR.

Main Outcome Measures  The diagnostic accuracy of differentially expressed genes as determined by the area under the receiver operating characteristic curve (AUC).

Results  We found 37 genes differentially expressed by 8-fold higher or lower. Fifteen genes were downregulated and 22 were upregulated in adrenocortical carcinoma. Of the 37 genes, 29 differentially expressed by microarray correlated with the gene expression levels by quantitative RT-PCR (P  .01). Of the 37 genes validated by RT-PCR, 22 were significantly differentially expressed between benign and malignant adrenocortical tumors (P < .05). Five of these 22 genes had an AUC of 0.80 or greater (the AUC for IL13RA2 was 0.90; HTR2B, 0.87; CCNB2, 0.86; RARRES2, 0.86; and SLC16A9, 0.80), indicating high diagnostic accuracy for distinguishing benign from malignant adrenocortical tumors.

Conclusion  We identified 37 genes that are dysregulated in adrenocortical carcinoma, and several of the differentially expressed genes have excellent diagnostic accuracy for distinguishing benign from malignant adrenocortical tumors.

Author Affiliations: Departments of Surgery (Drs Fernandez-Ranvier, Suh, Duh, Clark, and Kebebew and Ms Weng), Epidemiology and Biostatistics (Dr Yeh), and Pathology (Dr Khanafshar), J. David Gladstone Institutes Genomics Core Laboratory (Dr Barker), and UCSF Helen Diller Family Comprehensive Cancer Center (Drs Clark and Kebebew), University of California, San Francisco.

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