Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.
Endocr J. 2011;58(7):527-34. doi: 10.1507/endocrj.k11e-026. Epub 2011 Apr 27.
Adrenocortical carcinoma (ACC) is a very rare malignant tumor with poor prognosis. To gain insight into the pathogenic significance of ACC, we studied clinicopathological features and gene expression profile in ACC. We analyzed five ACC cases (two men and three women) with the median age of 45-year-old who underwent adrenalectomy at our institute. Endocrine studies revealed that two cases had subclinical Cushing's syndrome (SCS) and one with concomitant estrogen-secreting tumor, while the rest of three cases had non-functioning tumors. Analysis of urinary steroids profile by gas chromatography/mass spectrometry showed increased metabolites of corticosteroid precursors, such as 17-OH pregnenolone, 17-OH progesterone, dehydroepiandorosterone (DHEA), and 11-deoxycortisol in all five cases. The pathological diagnosis of ACC was based on Weiss's criteria with its score ≥ 3. The mean size of the resected tumors was 87 mm and Ki67/MIB1 labeling index, a proliferative marker, was 3-27%. Immunohistochemical analysis revealed a disorganized expression of several steroidogenic enzymes, such as 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase, and DHEA-sulfotransferase. Among several genes determined by RT-PCR, insulin-like growth factor (IGF)-II mRNA was consistently and abundantly expressed in all 5 tumor tissues. Postoperatively, two cases with SCS developed local recurrence and liver metastasis. The present study suggests that the disorganized expression of steroidogenic enzymes and the overexpression of IGF-II by the tumor are hallmarks of ACC, which could be used as biochemical and molecular markers for ACC.
肾上腺皮质癌 (ACC) 是一种预后极差的罕见恶性肿瘤。为了深入了解 ACC 的发病机制，我们研究了 ACC 的临床病理特征和基因表达谱。我们分析了在我院接受肾上腺切除术的 5 例 ACC 病例（2 例男性，3 例女性），中位年龄为 45 岁。内分泌研究显示，2 例存在亚临床库欣综合征（SCS），1 例同时伴有雌激素分泌肿瘤，而其余 3 例为无功能肿瘤。通过气相色谱/质谱法分析尿甾体谱显示，所有 5 例患者的皮质类固醇前体代谢物均增加，如 17-羟孕烯醇酮、17-羟孕酮、脱氢表雄酮（DHEA）和 11-脱氧皮质醇。根据 Weiss 标准，ACC 的病理诊断得分为≥3 分。切除肿瘤的平均大小为 87mm，增殖标志物 Ki67/MIB1 标记指数为 3-27%。免疫组织化学分析显示，几种甾体生成酶的表达紊乱，如 3β-羟类固醇脱氢酶、17α-羟化酶和 DHEA-硫酸转移酶。通过 RT-PCR 确定的几个基因中，胰岛素样生长因子 (IGF)-II mRNA 在所有 5 个肿瘤组织中均持续且大量表达。术后，2 例 SCS 患者出现局部复发和肝转移。本研究表明，甾体生成酶的紊乱表达和肿瘤中 IGF-II 的过度表达是 ACC 的特征，可作为 ACC 的生化和分子标志物。
