Department of Oncology, University of Turin at San Luigi Hospital, Orbassano, 10043, Torino, Italy.
Department of Clinical & Biological Sciences, University of Turin at San Luigi Hospital, Orbassano, 10043, Torino, Italy.
Hum Pathol. 2014 Aug;45(8):1555-62. doi: 10.1016/j.humpath.2014.04.005. Epub 2014 Apr 24.
Several microRNAs (miRNAs) were shown to be deregulated in adrenocortical carcinoma (ACC) as compared with adenoma, but a detailed assessment of their expression in its histologic variants and correlation with clinicopathologic characteristics has not been performed, so far. Our aim was to assess the expression of 5 selected miRNAs (IGF2 gene-related miR-483-3p and 5p and hypoxia-induced miR-210, miR-195, and miR-1974) in a series of 51 ACCs (35 classical, 6 myxoid, and 10 oncocytic) as compared with clinical and pathologic features and immunohistochemical expression of prognostic markers, including steroidogenic factor 1, p53, β-catenin, and glucose transporter 1. Oncocytic carcinomas had a reduced expression of miR-483-3p (P = .0325), miR-483-5p (P = .0175), and miR-210 (P = .0366), as compared with other histotypes. Overexpression of miR-210 was associated with the presence of necrosis (P = .0035), high Ki-67 index (P = .0013), and high glucose transporter 1 expression (P = .0043), whereas an inverse correlation with mitotic rate was observed in cases with high miR-493-3p (P = .0191) and miR-1974 (P = .0017) expression. High miR-1974 was also associated with low Ki-67 (P = .0312) and European Network for the Study of Adrenal Tumors stage (P = .0082) and negative p53 (P = .0013). At univariate analysis myxoid/classic histotype (P = .026), high miR-210 (P = .0465), high steroidogenic factor 1 protein (P = .0017), high Ki-67 (P = .0066), and high mitotic index (P = .0006) were significantly associated the shorter overall survival, the latter being the sole independent prognostic factor at multivariate analysis (P = .017). In conclusion, (a) miR-483-3p, miR-483-5p, and miR-210 are differentially expressed in ACC variants, and (b) high miR-210 is associated with clinicopathologic parameters of aggressiveness and a poor prognosis.
几种 microRNAs（miRNAs）在肾上腺皮质癌（ACC）中与腺瘤相比被证明存在失调，但迄今为止，尚未对其在组织学变异中的表达进行详细评估及其与临床病理特征的相关性。我们的目的是评估 5 种选定的 miRNA（与 IGF2 基因相关的 miR-483-3p 和 5p 以及缺氧诱导的 miR-210、miR-195 和 miR-1974）在 51 例 ACC（35 例经典型、6 例黏液样型和 10 例嗜酸性细胞型）中的表达情况，并与临床病理特征和预后标志物的免疫组织化学表达进行比较，包括类固醇生成因子 1、p53、β-连环蛋白和葡萄糖转运蛋白 1。与其他组织类型相比，嗜酸性细胞瘤中 miR-483-3p（P =.0325）、miR-483-5p（P =.0175）和 miR-210 的表达减少。miR-210 的过表达与坏死的存在有关（P =.0035）、高 Ki-67 指数（P =.0013）和高葡萄糖转运蛋白 1 表达（P =.0043），而在高 miR-493-3p（P =.0191）和 miR-1974（P =.0017）表达的病例中，与有丝分裂率呈负相关。高 miR-1974 也与低 Ki-67（P =.0312）和欧洲肾上腺肿瘤研究网络分期（P =.0082）以及阴性 p53（P =.0013）相关。在单因素分析中，黏液样/经典组织学类型（P =.026）、高 miR-210（P =.0465）、高类固醇生成因子 1 蛋白（P =.0017）、高 Ki-67（P =.0066）和高有丝分裂指数（P =.0006）与总生存率缩短显著相关，后者是多因素分析中的唯一独立预后因素（P =.017）。总之，（a）miR-483-3p、miR-483-5p 和 miR-210 在 ACC 变异体中表达不同，（b）高 miR-210 与侵袭性和预后不良的临床病理参数相关。
