cHCC‐CCA

Brunt, Elizabeth M.; Aishima, Shinichi; Clavien, Pierre Alain; Fowler, Kathryn J.; Goodman, Zachary; Gores, Gregory J.; Gouw, Annette S.H.; Kagen, Alex; Klimstra, David S.; Komuta, Mina; Kondo, Fukuo; Miksad, Rebecca A.; Nakano, Masayuki; Nakanuma, Yasuni; Ng, Irene Ol; Paradis, Valérie; Park, Young Nyun; Quaglia, Alberto; Roncalli, Massimo; Roskams, Tania; Sakamoto, Michiie; Saxena, Romil; Sempoux, Christine; Sirlin, Claude B.; Stueck, Ashley; Thung, Swan N.; Tsui, Wilson M. S.; Wang, Xin Wei; Wee, Aileen; Yano, Hirohisa; Yeh, Matthew M.; Zen, Yoh; Zucman‐Rossi, Jessica; Theise, Neil D.

doi:10.1002/hep.29789

Cited by 282 publications

(314 citation statements)

References 57 publications

(179 reference statements)

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“…Both scirrhous type HCC and K7‐ or K19‐positive HCC can be differential diagnoses of INT; however, these tumors mainly have typical HCC cell forms and can be differentiated with careful morphological observation . Additionally, due to wide structural diversities, such as strands and gland‐like structures and marked desmoplastic stroma, INT could be misdiagnosed as iCCA . In the pathological diagnosis in CHC, IHC staining is helpful, but not essential.…”

Section: Discussionmentioning

confidence: 99%

“…Usually, mucin production is absent, and marked desmoplastic or acellular hyalinized stroma are observed. Even though immunohistochemical stains provide supplementary evidence, INT cells express both hepatocytic and cholangiocytic markers to various degrees . Furthermore, INT could be combined with HCC, iCCA, and other stem‐cell feature subtypes …”

Section: Introductionmentioning

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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

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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“…However, CHC often contains various components, and it is difficult to clearly classify CHC clinically. Therefore, in the consensus paper published in 2018 and the new WHO classification published in 2019, the subtypes were abolished and the current guidelines indicate that primary liver carcinomas with both hepatocellular and cholangiocytic differentiation within the same tumor is CHC . Thus, stem cell phenotypes/features might be present in CHC, but it is not sufficient for diagnosis of CHC.…”

Section: Introductionmentioning

confidence: 99%

CD133 and epithelial cell adhesion molecule expressions in the cholangiocarcinoma component are prognostic factors for combined hepatocellular cholangiocarcinoma

Wakizaka

Yokoo

Kamiyama

et al. 2019

Hepatology Research

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Aim A new classification of combined hepatocellular cholangiocarcinoma (CHC) was recently reported. Cancer stem cells have been associated with CHC carcinogenesis. This study examined the association of cancer stem cell marker expression and prognosis in CHC classified using the new classification. Methods We enrolled 26 CHC patients and classified them according to the new classification. We evaluated the expression of cancer stem cell markers (CD56, CD133, and epithelial cell adhesion molecule [EpCAM]) by immunohistochemical staining in each component. We analyzed the association between expressions and prognosis. Results Seven cases were hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) (cHCC‐CCA), 12 were HCC and intermediate cell carcinoma (HCC‐INT), and seven were intermediate cell carcinoma (INT). The CD133‐positive rate tended to be higher in the CCA (42.9%) and INT component (50.0%) than the HCC component (14.3%) in cHCC‐CCA. In HCC‐INT, the CD133‐positive rate in the INT component (83.3%) was significantly higher than the HCC component (8.3%; P = 0.001). For EpCAM, the positive rate in the CCA component (71.4%) and INT component (50.0%) tended to be higher than the HCC component (14.3%) in cHCC‐CCA. Overall survival and disease‐free survival were significantly worse in cases with CD133‐positive (P = 0.048 and P = 0.048, respectively) or EpCAM‐positive (P = 0.041 and P = 0.041, respectively) CCA component in cHCC‐CCA. Conclusions INT and CCA components showed higher expression rates of cancer stem cell markers than the HCC component. CD133 or EpCAM expression in the CCA component was associated with poor prognosis in cHCC‐CCA.

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“…Primary hepatic cancers which display both hepatocellular and cholangiocytic elements are referred to as ‘combined’ or ‘mixed’ hepatocellular-cholangiocarcinoma 21. Studies which have evaluated the prevalence of these tumours suggest that they comprise between 2% and 5% of all primary liver malignancies,12 22–25 and interestingly, they have been reported to occur in both cirrhotic and non-cirrhotic livers 25–27.…”

Section: Tumour Types Treated With Neoadjuvant Therapymentioning

confidence: 99%

“…Of note, there is minimal evidence evaluating liver transplantation and the use of neoadjuvant therapy in these tumours; when these tumours are found in hepatic explants, it is typically incidental in nature or are from patients who were misdiagnosed as having traditional HCC 28. As discussed by Brunt et al , there is a need to study the outcome of these mixed tumours following hepatic transplantation as well as their response to various locoregional therapies and modern targeted treatments 21. To date, only small series have evaluated these issues 29 30…”

Section: Tumour Types Treated With Neoadjuvant Therapymentioning

confidence: 99%

Gross and microscopic changes of liver neoplasms and background hepatic structures following neoadjuvant therapy

Hodgson

Al-Mansouri²,

Adeyi³

et al. 2019

J Clin Pathol

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Liver transplantation is a surgical option with curative intent used in the management of some cases of hepatocellular carcinoma and cholangiocarcinoma (hilar, rarely intrahepatic). A number of different therapeutic modalities including ablative techniques, arterially directed therapies, radiation and chemotherapy are used in the neoadjuvant setting prior to liver transplantation with the goals of preventing tumour progression, decreasing post-transplant recurrence and possibly downstaging patients with tumour burden beyond what is acceptable by current transplant criteria. Pathologists evaluating hepatic explants must be aware of these neoadjuvant therapies and the alterations induced by them in both tumourous and non-tumourous tissue. In this review, we discuss common neoadjuvant therapies used in in this setting, as well as the gross and microscopic changes induced by these presurgical treatments within hepatic neoplasms as well as the background hepatic parenchyma and nearby structures. Select secondary tumours involving the liver which are pretreated will also be discussed. Finally, proper reporting of these changes will be mentioned.

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cHCC‐CCA

Abstract: It is recommended that diagnosis is based on routine histopathology with hematoxylin and eosin (H&E); immunostains are supportive, but not essential for diagnosis. (Hepatology 2018;68:113-126).

Cited by 282 publications

References 57 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

CD133 and epithelial cell adhesion molecule expressions in the cholangiocarcinoma component are prognostic factors for combined hepatocellular cholangiocarcinoma

Gross and microscopic changes of liver neoplasms and background hepatic structures following neoadjuvant therapy

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