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Cancer stem cells in primary liver cancers: pathological concepts and imaging findings.

Joo I, Kim H, Lee JM - Korean J Radiol (2015)

Bottom Line: There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth.Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes.Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Seoul National University Hospital, Seoul 110-744, Korea.

ABSTRACT
There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations. In this article, we reviewed the recent concepts of CSCs in the development of primary liver cancers, focusing on their pathological and radiological findings. Awareness of the pathological concepts and imaging findings of primary liver cancers with features of CSCs is critical for accurate diagnosis, prediction of outcome, and appropriate treatment options for patients.

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Hepatocellular carcinoma with "stemness"-marker expression in 48-year-old male patient with liver cirrhosis.A-C. Gadoxetic acid-enhanced MRI showing irregular mass (arrows) in segment 6 of liver with tumor thrombus (arrowheads) in right inferior hepatic vein. Mass shows peripheral enhancement on arterial phase (A) and delayed enhancement (B). C. Hepatobiliary phase showing mass with hypointensity. D. Gross examination reveals infiltrative solid greyish-white mass in liver. E. Tumor cells with eosinophilic cytoplasm arranged in sheets and pseudoglandular structures (H&E stain, × 400). F. Immunohistochemical staining revealing K19-positive cells in tumor (× 400).
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Figure 9: Hepatocellular carcinoma with "stemness"-marker expression in 48-year-old male patient with liver cirrhosis.A-C. Gadoxetic acid-enhanced MRI showing irregular mass (arrows) in segment 6 of liver with tumor thrombus (arrowheads) in right inferior hepatic vein. Mass shows peripheral enhancement on arterial phase (A) and delayed enhancement (B). C. Hepatobiliary phase showing mass with hypointensity. D. Gross examination reveals infiltrative solid greyish-white mass in liver. E. Tumor cells with eosinophilic cytoplasm arranged in sheets and pseudoglandular structures (H&E stain, × 400). F. Immunohistochemical staining revealing K19-positive cells in tumor (× 400).

Mentions: In addition to microscopy which can readily used to identify cHCC-CCs, some morphologically typical HCCs may also show expressions of "stemness"-related markers, also known as HCCs with HPC immunophenotype (57) characterized by the expression of "stemness"-related markers, such as K19 (Fig. 9), CD133, and EpCAM. In > 5% of tumor cells, HCCs with these markers are associated with poorer prognosis compared to usual HCCs without these markers (58). HCCs with "stemness"-related markers are characterized by more frequent microvascular invasion, fibrous stroma, and less tumor pseudocapsule formation compared to conventional HCCs. They are known to behave aggressively, with higher stages at diagnosis and decreased overall survival rates (58). Associations between K19 expression and increased epithelial-mesenchymal transition-related proteins have been demonstrated in both Korean and Caucasian cohorts (58, 59). A recent Japanese study demonstrated that K19 expression in HCCs at liver biopsy was an indicator of high tumor recurrence rate after radiofrequency ablation (60). The frequency of K19 expression in HCCs varies from 4% (60) to 28% (58), depending on the cohort studied, the type of specimens used (resections, biopsies or tissue microarray cores), and the cut-off values determined for "positivity" (5% vs. 1%).


Cancer stem cells in primary liver cancers: pathological concepts and imaging findings.

Joo I, Kim H, Lee JM - Korean J Radiol (2015)

Hepatocellular carcinoma with "stemness"-marker expression in 48-year-old male patient with liver cirrhosis.A-C. Gadoxetic acid-enhanced MRI showing irregular mass (arrows) in segment 6 of liver with tumor thrombus (arrowheads) in right inferior hepatic vein. Mass shows peripheral enhancement on arterial phase (A) and delayed enhancement (B). C. Hepatobiliary phase showing mass with hypointensity. D. Gross examination reveals infiltrative solid greyish-white mass in liver. E. Tumor cells with eosinophilic cytoplasm arranged in sheets and pseudoglandular structures (H&E stain, × 400). F. Immunohistochemical staining revealing K19-positive cells in tumor (× 400).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4296278&req=5

Figure 9: Hepatocellular carcinoma with "stemness"-marker expression in 48-year-old male patient with liver cirrhosis.A-C. Gadoxetic acid-enhanced MRI showing irregular mass (arrows) in segment 6 of liver with tumor thrombus (arrowheads) in right inferior hepatic vein. Mass shows peripheral enhancement on arterial phase (A) and delayed enhancement (B). C. Hepatobiliary phase showing mass with hypointensity. D. Gross examination reveals infiltrative solid greyish-white mass in liver. E. Tumor cells with eosinophilic cytoplasm arranged in sheets and pseudoglandular structures (H&E stain, × 400). F. Immunohistochemical staining revealing K19-positive cells in tumor (× 400).
Mentions: In addition to microscopy which can readily used to identify cHCC-CCs, some morphologically typical HCCs may also show expressions of "stemness"-related markers, also known as HCCs with HPC immunophenotype (57) characterized by the expression of "stemness"-related markers, such as K19 (Fig. 9), CD133, and EpCAM. In > 5% of tumor cells, HCCs with these markers are associated with poorer prognosis compared to usual HCCs without these markers (58). HCCs with "stemness"-related markers are characterized by more frequent microvascular invasion, fibrous stroma, and less tumor pseudocapsule formation compared to conventional HCCs. They are known to behave aggressively, with higher stages at diagnosis and decreased overall survival rates (58). Associations between K19 expression and increased epithelial-mesenchymal transition-related proteins have been demonstrated in both Korean and Caucasian cohorts (58, 59). A recent Japanese study demonstrated that K19 expression in HCCs at liver biopsy was an indicator of high tumor recurrence rate after radiofrequency ablation (60). The frequency of K19 expression in HCCs varies from 4% (60) to 28% (58), depending on the cohort studied, the type of specimens used (resections, biopsies or tissue microarray cores), and the cut-off values determined for "positivity" (5% vs. 1%).

Bottom Line: There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth.Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes.Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Seoul National University Hospital, Seoul 110-744, Korea.

ABSTRACT
There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations. In this article, we reviewed the recent concepts of CSCs in the development of primary liver cancers, focusing on their pathological and radiological findings. Awareness of the pathological concepts and imaging findings of primary liver cancers with features of CSCs is critical for accurate diagnosis, prediction of outcome, and appropriate treatment options for patients.

Show MeSH
Related in: MedlinePlus