Soon P S H, Gill A J, Benn D E, Clarkson A, Robinson B G, McDonald K L, Sidhu S B
Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, St Leonards, Sydney, New South Wales 2065, Australia.
Endocr Relat Cancer. 2009 Jun;16(2):573-83. doi: 10.1677/ERC-08-0237. Epub 2009 Feb 13.
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.
肾上腺皮质肿瘤（ACTs）的管理很复杂。魏斯评分是目前ACT诊断中使用最广泛的系统。ACT的评分从0到9，分数越高，恶性程度越高。然而，评分3的ACT在表型上可能是良性或恶性的。我们的目标是通过对一组肾上腺皮质癌（ACCs）和肾上腺皮质腺瘤（ACAs）进行微阵列分析，以识别可作为魏斯评分辅助手段的鉴别基因。使用Affymetrix HGU133plus2.0基因芯片对一组经魏斯评分定义的ACC和ACA进行分析。通过单变量和多变量分析确定具有高鉴别力的基因，并通过定量实时逆转录PCR和免疫组织化学（IHC）进行确认。与ACA相比，IGF2、MAD2L1和CCNB1在ACC中的表达显著更高，而ABLIM1、NAV3、SEPT4和RPRM的表达显著更低。包括IGF2、MAD2L1、CCNB1和Ki-67在内的几种蛋白质在区分ACC和ACA方面具有较高的诊断准确性。然而，将IGF2和Ki-67联合使用时效果最佳，在诊断ACC时灵敏度为96%，特异性为100%。微阵列基因表达分析能准确区分ACC和ACA。IGF2和Ki-67免疫组化联合使用在区分这两组时也具有很高的准确性，对魏斯评分为3的ACT尤其有帮助。
