title: Differential diagnosis of hepatocellular carcinoma from metastatic tumors in the liver using microRNA expression.
abstract: Distinguishing hepatocellular carcinoma from metastatic tumors in the liver is of great practical importance, with significant therapeutic and prognostic implications. This differential diagnosis can be difficult because metastatic cancers in the liver, especially adenocarcinomas, may mimic the morphology and immunoexpression of hepatocellular carcinoma. Biomarkers that are specifically expressed in either hepatocellular carcinoma or metastatic adenocarcinoma can therefore be useful diagnostic tools. To find such biomarkers, we studied microRNA expression in 144 tumor samples using custom microarrays. Hsa-miR-141 and hsa-miR-200c, microRNAs that promote epithelial phenotypes, had significantly higher levels in non-hepatic epithelial tumors. In contrast, endothelial-associated hsa-miR-126 showed higher expression levels in hepatocellular carcinomas. Combinations of these microRNAs accurately identified primary hepatocellular carcinoma from metastatic adenocarcinoma in the liver. These findings were validated using quantitative real-time PCR to measure microRNA expression in additional samples. Thus, the tissue-specific expression patterns of microRNAs make them useful biomarkers for the diagnosis of liver malignancies.
authors.affiliation: Department of Pathology, Sheba Medical Center, Tel-Hashomer, 52621, Israel. barshack@sheba.health.gov.il
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.forename: Eti
authors.initials: E
authors.lastname: Meiri
authors.forename: Shai
authors.initials: S
authors.lastname: Rosenwald
authors.forename: Danit
authors.initials: D
authors.lastname: Lebanony
authors.forename: Meital
authors.initials: M
authors.lastname: Bronfeld
authors.forename: Sarit
authors.initials: S
authors.lastname: Aviel-Ronen
authors.forename: Kinneret
authors.initials: K
authors.lastname: Rosenblatt
authors.forename: Sylvie
authors.initials: S
authors.lastname: Polak-Charcon
authors.forename: Ilit
authors.initials: I
authors.lastname: Leizerman
authors.forename: Meital
authors.initials: M
authors.lastname: Ezagouri
authors.forename: Merav
authors.initials: M
authors.lastname: Zepeniuk
authors.forename: Norberto
authors.initials: N
authors.lastname: Shabes
authors.forename: Lahav
authors.initials: L
authors.lastname: Cohen
authors.forename: Sarit
authors.initials: S
authors.lastname: Tabak
authors.forename: Dalia
authors.initials: D
authors.lastname: Cohen
authors.forename: Zvi
authors.initials: Z
authors.lastname: Bentwich
authors.forename: Nitzan
authors.initials: N
authors.lastname: Rosenfeld
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D003937:Diagnosis, Differential; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs