Abstract
Background/Aims
Recent evidence of hepatic progenitor cells with the bipotential to differentiate
into hepatocytes and cholangiocytes gives rise to the suggestion that primary hepatic
carcinomas with features intermediate between hepatocellular carcinoma (HCC) and cholangiocarcinoma
(CC) may originate from hepatic progenitor cells.
Methods
Fifty-four cases of primary liver carcinomas were selected and an immunohistochemical
analysis was performed using hepatocytic markers (α-fetoprotein, hepatocyte), cholangiocytic
markers (carcinoembryonic antigen, cytokeratin 19) and progenitor cell marker (c-kit).
Results
Thirteen cases designated ‘intermediate’ carcinomas demonstrated strands/trabeculae
of small, uniform, round-to-oval cells with scanty cytoplasm and hyperchromatic nuclei
embedded within a thick desmoplastic stroma. Six were designated transitional type
combined hepatocellular-cholangiocarcinoma (CHC). Ten were named HCC small cell type,
demonstrating similar features to typical HCC, but composed of smaller cells. Simultaneous
expression of hepatocytic and cholangiocytic markers was demonstrated in 8/13 (61.5%),
4/6 (66.7%), and 3/10 (30%) cases of intermediate carcinomas, transitional CHCs, and
HCC small cell type, respectively, and c-kit expression was noted in 10/13 (76.9%), 4/6 (66.7%) and 7/10 (70%) cases, in the same
order.
Conclusions
Intermediate carcinoma may be a distinct type of primary liver carcinoma, morphologically
and phenotypically intermediate between HCC and CC, which originates from transformed
hepatic progenitor cells.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of HepatologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study.Cancer. 1985; 55: 124-135
- An immunohistochemical analysis of 13 cases with combined hepatocellular and cholangiocellular carcinoma.Liver. 1995; 15: 9-15
- A clinicopathological study on combined hepatocellular and cholangiocarcinoma.J Gastroenterol Hepatol. 1996; 11: 758-764
- Combined hepatocellular-cholangiocarcinoma: a histopathologic, immunohistochemical, and in situ hybridization study.Am J Surg Pathol. 2002; 26: 989-997
- Primary liver tumour of intermediate (hepatocyte-bile duct cell) phenotype: a progenitor cell tumour?.Liver. 1998; 18: 288-293
- Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers: clinical and biological implications.Am J Pathol. 1996; : 1167-1175
- Hepatocellular carcinoma expressing both hepatocellular and biliary markers also expresses cytokeratin 14, a marker of bipotential progenitor cells.J Hepatol. 1999; 31: 965-966
- Heterogeneity and plasticity of hepatocyte lineage cells.Hepatology. 2001; 33: 738-750
- Immunolocalization of OV-6, a putative progenitor cell marker in human fetal and diseased pediatric liver.Hepatology. 1998; 28: 980-985
- Hepatic OV-6 expression in human liver disease and rat experiments: evidence for hepatic progenitor cells in man.J Hepatol. 1998; 291: 455-463
- Immunohistochemical evidence for hepatic progenitor cells in liver diseases.Liver. 2002; 22: 365-373
- Occurrence of oval-type cells in hepatitis B virus-associated human hepatocarcinogenesis.Hepatology. 1992; 16: 1327-1333
- Deep intralobular extension of human hepatic progenitor cells correlates with parenchymal inflammation in chronic viral hepatitis: can progenitor cells migrate?.J Pathol. 2000; 192: 373-378
- The immunohistochemical phenotype of dysplastic foci in human liver: correlation with putative progenitor cells.J Hepatol. 2000; 33: 76-84
- Oval cell numbers in human chronic liver diseases are directly related to disease severity.Am J Pathol. 1999; 143: 537-541
- Identification of bipotential progenitor cells in human liver development.Hepatology. 1996; 23: 476-481
- Update on hepatic stem cells.Liver. 2001; 21: 367-373
- Hepatocytes from non-hepatic adult stem cells.Nature. 2000; 406: 257
- Hepatic stem cells: from bone marrow cells to hepatocytes.Biochem Biophys Res Commun. 2001; 281: 1-5
- Stem cells and rat liver carcinogenesis: contributions of confocal and electron microscopy.J Histochem Cytochem. 1998; 46: 613-626
- Hepatic ‘stem’ cells: coming full circle.Blood Cells Mol Dis. 2001; 27: 590-600
- Bone marrow as a potential source of hepatic oval cells.Science. 1999; 284: 1168-1170
- Liver from bone marrow in humans.Hepatology. 2000; 32: 11-16
- Hepatic stem cells: a review.Pathology. 2001; 33: 130-141
- Expression of stem cell receptor c-kit in normal and diseased pediatric liver.Hepatology. 1999; 30: 112-117
- Human hepatic stem-like cells isolated using c-kit or CD34 can differentiate into biliary epithelium.Gastroenterology. 2001; 120: 534-544
- The canals of Hering and hepatic stem cells in humans.Hepatology. 1999; 30: 1425-1433
- Hepatocyte antigen as a marker of hepatocellular carcinoma: an immunohistochemical comparison to carcinoembryonic antigen, CD10, and alpha-fetoprotein.Am J Surg Pathol. 2002; 26: 978-988
- Clinicopathologic study on cholangiolocellular carcinoma.Oncol Rep. 2001; 8: 263-268
- Expression of biliary antigen and its clinical significance in hepatocellular carcinoma.Yonsei Med J. 1999; 5: 472-477
Article info
Publication history
Accepted:
October 15,
2003
Received in revised form:
September 8,
2003
Received:
May 16,
2003
xIdentification
Copyright
© 2003 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
