title: MicroRNA expression patterns in adrenocortical carcinoma variants and clinical pathologic correlations.
abstract: 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.
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Orbassano, 10043, Torino, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Duregon
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Orbassano, 10043, Torino, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Rapa
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Orbassano, 10043, Torino, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Votta
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Orbassano, 10043, Torino, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Giorcelli
authors.affiliation: Department of Clinical & Biological Sciences, University of Turin at San Luigi Hospital, Orbassano, 10043, Torino, Italy.
authors.forename: Fulvia
authors.initials: F
authors.lastname: Daffara
authors.affiliation: Department of Clinical & Biological Sciences, University of Turin at San Luigi Hospital, Orbassano, 10043, Torino, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Terzolo
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Orbassano, 10043, Torino, Italy.
authors.forename: Giorgio V
authors.initials: GV
authors.lastname: Scagliotti
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Orbassano, 10043, Torino, Italy. Electronic address: marco.volante@unito.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Orbassano, 10043, Torino, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D055815:Young Adult
chemical_list: C552722:MIRN195 microRNA, human; C543800:MIRN210 microRNA, human; C548912:MIRN483 microRNA, human; D035683:MicroRNAs
keywords: Adrenal cortex; Carcinoma; Prognosis; Variant; microRNA