Institute of Pathology and Neuropathology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
J Clin Pathol. 2011 Jun;64(6):529-35. doi: 10.1136/jcp.2010.085621. Epub 2011 Apr 6.
For the clinical management of adrenocortical neoplasms it is crucial to correctly distinguish between benign and malignant tumours. Even histomorphologically based scoring systems do not allow precise separation in single lesions, thus novel parameters are desired which offer a more accurate differentiation. The tremendous potential of microRNAs (miRNAs) as diagnostic biomarkers in surgical pathology has recently been shown in a broad variety of tumours.
In order to elucidate the diagnostic impact of miRNA expression in adrenocortical neoplasms, a cohort of 20 adrenocortical specimens including normal adrenal tissue (n=4), adrenocortical adenomas (ACAs) (n=9), adrenocortical carcinomas (ACCs) (n=4) and metastases (n=3) was analysed using TaqMan low density arrays to identify specific miRNA profiles in order to distinguish between benign and malignant adrenocortical lesions. Results were validated in a validation cohort (n=16).
Concerning the differential diagnosis of ACAs and ACCs, 159 out of 667 miRNAs were up- and 89 were down-regulated in ACAs. Using real-time PCR analysis of three of the most significantly expressed single key miRNAs allowed separation of ACAs from ACCs. ACCs exhibited significantly lower levels of miR-139-3p (up to 8.49-fold, p<0.001), miR-675 (up to 23.25-fold, p<0.001) and miR-335 (up to 5.25-fold, p<0.001). A validation cohort of 16 specimen with known Weiss score showed up-regulation of miR-335 and miR-675 in the majority of cases with probable malignant course, although overlapping values exist.
miRNA profiling of miR-675 and miR-335 helps in discriminating ACCs from ACAs. miRNA analysis may indicate malignant behaviour in cases with indeterminate malignant potential.
对于肾上腺皮质肿瘤的临床管理，正确区分良性和恶性肿瘤至关重要。即使基于组织形态学的评分系统也不能在单个病变中进行精确区分，因此需要寻找新的参数来进行更准确的区分。微小 RNA（miRNA）作为外科病理学诊断生物标志物的巨大潜力在多种肿瘤中得到了广泛的证实。
为了阐明 miRNA 在肾上腺皮质肿瘤中的诊断作用，我们分析了 20 个肾上腺皮质标本，包括正常肾上腺组织（n=4）、肾上腺皮质腺瘤（ACAs）（n=9）、肾上腺皮质癌（ACCs）（n=4）和转移（n=3），使用 TaqMan 低密度阵列来识别特定的 miRNA 谱，以区分良性和恶性肾上腺皮质病变。结果在验证队列（n=16）中进行了验证。
在 ACA 和 ACC 的鉴别诊断方面，667 个 miRNA 中有 159 个上调，89 个下调。使用实时 PCR 分析三个最显著表达的单个关键 miRNA 可以将 ACA 与 ACC 分开。ACC 表现出明显更低水平的 miR-139-3p（高达 8.49 倍，p<0.001）、miR-675（高达 23.25 倍，p<0.001）和 miR-335（高达 5.25 倍，p<0.001）。一个已知 Weiss 评分的 16 个标本的验证队列显示，在大多数可能恶性的病例中，miR-335 和 miR-675 上调，尽管存在重叠值。
miR-675 和 miR-335 的 miRNA 谱分析有助于区分 ACC 和 ACA。miRNA 分析可能表明具有不确定恶性潜能的病例存在恶性行为。
