Malic enzyme 1 is a potential marker of combined hepatocellular cholangiocarcinoma, subtype with stem‐cell features, intermediate‐cell type

作者: Yutaro Mihara , Jun Akiba , Sachiko Ogasawara , Reiichiro Kondo , Hiroto Fukushima

DOI: 10.1111/HEPR.13365

关键词: Receiver operating characteristicPathologyGene expressionHepatocellular carcinomaKeratinImmunohistochemistryMicroarray analysis techniquesMedicineIntrahepatic CholangiocarcinomaINT

摘要: Aim Combined hepatocellular cholangiocarcinoma, subtype with stem-cell features, intermediate-cell (INT) shows various histological appearances and could be misdiagnosed as intrahepatic cholangiocarcinoma (iCCA). In the present study, we aimed to identify specific diagnostic markers of INT. Methods We extracted RNA from FFPE sections six INT, five iCCA, carcinoma (HCC) cases compared gene expression between HCC by microarray analysis. then undertook immunohistochemical (IHC) staining potential key molecules identified analysis, conventional hepatocytic marker, hepatocyte paraffin (HepPar)-1, cholangiocytic markers, keratin (K) 7 K19, on 35 25 60 cases. Results Microarray analysis suggested that malic enzyme 1 (ME1) was significantly upregulated in Immunohistochemical revealed positive rates ME1 were 77.1% (27/35), 28.0% (7/25), 61.7% (37/60), respectively. Analysis classification regression trees based IHC scores indicated HepPar-1 a good candidate for discriminating others high sensitivity (93.3%) specificity (96.7%). A multiple logistic model receiver operating characteristic curve ME1, K7, K19 generated composite score can discriminate INT iCCA. Using this score, discriminated iCCA (88.6%) (88.0%). Conclusions propose is useful marker when used combination other markers.

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