Department of Anatomy and UMIB (Unit for Multidisciplinary Biomedical Research) of ICBASUniversity of Porto, Porto, 4050-313, Portugal Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP)Porto, 4200-465, Portugal Department of EndocrinologyHospital S.João, Porto, 4200-319, Portugal.
Endocr Connect. 2013 Aug 28;2(3):137-45. doi: 10.1530/EC-13-0025. Print 2013.
Malignant adrenocortical tumors (ACTs) are rare and highly aggressive; conversely, benign tumors are common and frequently found incidentally (the so-called incidentalomas). Currently, the use of molecular markers in the diagnosis of ACTs is still controversial. The aim of this study was to analyze the molecular profile of different ACTs with the purpose of identifying markers useful for differentiating between these tumors. The ACTs that were studied (n=31) included nonfunctioning adenomas (ACAn)/incidentalomas (n=13), functioning adenomas with Cushing's syndrome (ACAc) (n=7), and carcinomas (n=11); normal adrenal glands (n=12) were used as controls. For each sample, the percentage area stained for the markers StAR, IGF2, IGF1R, p53, MDM2, p21, p27, cyclin D1, Ki-67, β-catenin, and E-cadherin was quantified using a morphometric computerized tool. IGF2, p27, cyclin D1, and Ki-67 were the markers for which the percentage of stained area was significantly higher in carcinoma samples than in adenoma samples. Ki-67 and p27 were the markers that exhibited the highest discriminative power for differential diagnosis between carcinomas and all type of adenomas, while IGF2 and StAR were only found to be useful for differentiating between carcinomas and ACAn and between carcinomas and ACAc respectively. The usefulness of Ki-67 has been recognized before in the differential diagnosis of malignant tumors. The additional use of p27 as an elective marker to distinguish benign ACTs from malignant ACTs should be considered.
恶性肾上腺皮质肿瘤（ACT）罕见且高度侵袭性；相反，良性肿瘤常见且常偶然发现（所谓的偶发瘤）。目前，在 ACT 的诊断中使用分子标志物仍存在争议。本研究旨在分析不同 ACT 的分子谱，目的是确定有助于区分这些肿瘤的标志物。研究的 ACT 包括无功能腺瘤/偶发瘤（n=13）、库欣综合征功能性腺瘤（ACAc）（n=7）和癌（n=11）；正常肾上腺（n=12）作为对照。对于每个样本，使用形态计量计算机工具对 StAR、IGF2、IGF1R、p53、MDM2、p21、p27、cyclin D1、Ki-67、β-catenin 和 E-cadherin 等标志物的染色面积百分比进行定量。在癌样本中，IGF2、p27、cyclin D1 和 Ki-67 的染色面积百分比明显高于腺瘤样本。Ki-67 和 p27 是用于区分癌与所有类型腺瘤的最佳鉴别诊断标志物，而 IGF2 和 StAR 仅分别用于区分癌与 ACAn 和癌与 ACAc。Ki-67 在恶性肿瘤的鉴别诊断中之前已被认识到其有用性。应考虑将 p27 作为一种选择性标志物，用于区分良性和恶性 ACT。
