Whole-exome mutational and transcriptional landscapes of combined hepatocellular cholangiocarcinoma and intrahepatic cholangiocarcinoma reveal molecular diversity

Liu, Zhenhao; Lian, Baofeng; Dong, Qiongzhu; Sun, Han; Wei, Jie; Sheng, Yuan‐Yuan; Li, Wei; Li, Yixue; Xie, Lu; Liu, Lei; Qin, Lun–Xiu

doi:10.1016/j.bbadis.2018.01.027

Cited by 52 publications

(53 citation statements)

References 33 publications

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“…Liu et al . reported that TP53 , RYR3 , FBN2 , CTNNB1 , and ARID1A were mutated in CHC; however, the subtype of CHC was not mentioned. Sasaki et al .…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies reported that ME1 metabolism is regulated by a mutation of major oncogenes or antioncogenes, such as KRAS, myc, or TP53. 24,29,31,32,35 Liu et al reported that TP53, RYR3, FBN2, CTNNB1, and ARID1A were mutated in CHC; 36 however, the subtype of CHC was not mentioned. Sasaki et al also reported that CHC including INT showed mutation in KRAS, IDH1/2, ARID1A, TERT, and TP53.…”

Section: Discussionmentioning

confidence: 99%

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

Mihara

Akiba

Ogasawara

et al. 2019

Hepatology Research

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

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“…Liu et al . reported that TP53 , RYR3 , FBN2 , CTNNB1 , and ARID1A were mutated in CHC; however, the subtype of CHC was not mentioned. Sasaki et al .…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Mihara

Akiba

Ogasawara

et al. 2019

Hepatology Research

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“…Just as the histological aspects in cHCC-CCA vary, so does the molecular profile. 31,32,34,[36][37][38][39][40][41][42] Previous studies found that the genetics of cHCC-CCA were closer to iCCA than HCC. 42 However, the recent study performed by Joseph et al showed that the genetics of cHCC-CCA, classical type, are distinct from iCCA but similar to HCC, for example, alterations in TERT, TP53, cell cycle genes (CCND1, CCNE1, CDKN2A), receptor tyrosine kinase/Ras/PI3-kinase pathway genes (MET, ERBB2, KRAS, PTEN).…”

Section: Molecular Profiles (►Table 2)mentioning

confidence: 99%

A Review on the Update of Combined Hepatocellular Cholangiocarcinoma

Komuta

Yeh

2019

Semin Liver Dis

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Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a primary liver tumor with neoplastic components of both hepatocytic and cholangiocytic differentiation. This unique neoplasm is gaining increasing recognition due to the intriguing pathology, tumor biology, and clinical behavior. It also poses challenges in diagnosis, treatment, and research, largely because of its histological and phenotypic diversity that lead to confusion in terminology and classification. There have been efforts attempting to unify the terminology of this neoplasm recently. Advances in investigation in various aspects have also been made. This review aims to update the terminology, classification, and clinical and pathological characteristics of cHCC-CCA.

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“…cHCC-ICC studies integrating both genomics and transcriptomics using RNA-seq, WES and whole genome sequencing (WGS) find similar patterns in changes of key genes and tend to find more similarities between cHCC-ICC [especially Lisa and Allen type C (poorly defined transition) cHCC-ICC] and HCC, such as in TP53 and CTNNB1, rather than ICC (even ICCs arising in cirrhotic livers). Furthermore, molecular alterations characteristically seen in ICC, such as changes in PBRM1, IDH1, IDH2, FGFR2, and BAP1 were not present across cHCC-ICC (44,47,51).…”

Section: Genetic Characterization and Molecular Biologymentioning

confidence: 89%

Update on the Genetics of and Systemic Therapy Options for Combined Hepatocellular Cholangiocarcinoma

et al. 2020

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Combined hepatocellular-cholangiocarcinoma (cHCC-ICC) is an uncommon and aggressive form of primary liver cancer. Currently, there are no international guidelines for optimal management. For localized tumors, radical resection represents the preferred treatment option, whereas for advanced tumors, systemic therapies recommended for intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are often selected. Emerging information from comparative cohort studies, genomic and transcriptomic data sets are starting to build a case for rationalized approaches to systemic treatment in the advanced setting specific to cHCC-ICC.

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Whole-exome mutational and transcriptional landscapes of combined hepatocellular cholangiocarcinoma and intrahepatic cholangiocarcinoma reveal molecular diversity

Abstract: CHC and ICC are different subtypes of PLC. This study discusses predominantly the molecular genetic details of PLC subtypes and highlights the need for an accurate diagnosis and treatment of specific PLC subtypes to optimize patient management.

Cited by 52 publications

References 33 publications

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

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

A Review on the Update of Combined Hepatocellular Cholangiocarcinoma

Update on the Genetics of and Systemic Therapy Options for Combined Hepatocellular Cholangiocarcinoma

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