microRNA expression patterns in adrenocortical carcinoma variants and clinical pathologic correlations

Summary 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.