title: Microarray gene expression and immunohistochemistry analyses of adrenocortical tumors identify IGF2 and Ki-67 as useful in differentiating carcinomas from adenomas.
abstract: The management of adrenocortical tumors (ACTs) is complex. The Weiss score is the present 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 real-time reverse transcription PCR and immunohistochemistry (IHC). The expression of IGF2, MAD2L1, and CCNB1 were significantly higher in ACCs compared with 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 two groups and is particularly helpful in ACTs with Weiss score of 3.
authors.affiliation: Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, St Leonards, Sydney, New South Wales 2065, Australia. patsysoon@med.usyd.edu.au
authors.forename: P S H
authors.initials: PS
authors.lastname: Soon
authors.forename: A J
authors.initials: AJ
authors.lastname: Gill
authors.forename: D E
authors.initials: DE
authors.lastname: Benn
authors.forename: A
authors.initials: A
authors.lastname: Clarkson
authors.forename: B G
authors.initials: BG
authors.lastname: Robinson
authors.forename: K L
authors.initials: KL
authors.lastname: McDonald
authors.forename: S B
authors.initials: SB
authors.lastname: Sidhu
mesh_terms: D000293:Adolescent; D000302:Adrenal Cortex / Q000378:metabolism / Q000473:pathology; D018246:Adrenocortical Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D019394:Ki-67 Antigen / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C035170:IGF2 protein, human; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II