Potential conflict of interest: Nothing to report.
Cholangiocarcinoma: A cancer in search of the right classification†
Article first published online: 4 OCT 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 56, Issue 4, pages 1585–1586, October 2012
How to Cite
Cardinale, V., Carpino, G., Reid, L. M., Gaudio, E. and Alvaro, D. (2012), Cholangiocarcinoma: A cancer in search of the right classification. Hepatology, 56: 1585–1586. doi: 10.1002/hep.25705
- Issue published online: 4 OCT 2012
- Article first published online: 4 OCT 2012
- Accepted manuscript online: 12 MAR 2012 05:55AM EST
- Manuscript Accepted: 10 FEB 2012
- Manuscript Received: 9 FEB 2012
To the Editor:
We read with interest the article by Komuta et al.1 showing large differences in clinical-pathological features of intrahepatic cholangiocarcinomas (ICCs) arising from columnar mucin-producing cholangiocytes lining large bile ducts versus ones arising from cuboidal non mucin-producing cholangiocytes located in or near canals of Hering, comprised of human hepatic stem cells (hHpSCs) that are lineage-restricted to hepatocytes and cholangiocytes. These results are in keeping with previous studies dealing with the pathological, epidemiological, and clinical heterogeneity of cholangiocarcinomas (CCs)2, 3 and with the biological mechanisms underlying this heterogeneity.4 Indeed, Komuta et al. demonstrated that multiple cells of origin determine CC clinical-pathological differences and suggested that mixed-ICC and cholangiolocarcinoma (CLC) are completely separate entities with respect to the pure mucin-producing ICC (muc-ICC). Recently, Nakanuma and Sato5 provided evidence that peribiliary glands (PBGs) could be involved in the origin of intraductal papillary neoplasms of the bile duct, a preneoplastic lesion of muc-ICC. This confirms that human biliary tree stem cells (hBTSCs), residing in PBGs,6 are probable cells of origin of muc-ICCs. The results by Komuta et al.,1 together with advances with respect to stem cell biology,6, 7 and the relationship between tumor types and their normal stem cell counterparts,4 enable a CCs classification based on cells of origin. Hypothetically, the mixed-ICCs originate from cells from hHpSC-derived lineages,7 whereas pure mucin-producing CCs (intra- and extrahepatic) originate from hBTSC-derived lineages. Based on the grade of maturation of the cell of origin within the two lineages, CCs can be reclassified as:
CCs with focal hepatocytic differentiation from hHpSC-derived lineages: combined hepatocellular-cholangiocarcinoma, mixed-CC, and CCL.
Pure mucin-producing CCs from hBTSC-derived lineages in PBGs or from epithelium of intra- or extrahepatic large bile ducts: hilar CC and muc-ICC.
A CCs classification based on the cell-lineages-of-origin is more coherent with current knowledge on the epidemiology and risk factors and may have important clinical implications for the definition of specific therapeutic targets.
- 1Histological diversity in cholangiocellular carcinoma reflects the different cholangiocyte phenotypes. HEPATOLOGY 2012;55:1876-1888., , , , , , et al.
- 2Intra-hepatic and extra-hepatic cholangiocarcinoma: new insight into epidemiology and risk factors. World J Gastrointest Oncol 2010; 2: 407-416., , , , , , et al.
- 3Pathological classification of intrahepatic cholangiocarcinoma based on a new concept. World J Hepatol 2010; 2: 419-427., , , , , .
- 4Cells of origin in cancer. Nature 2011; 469: 314-322..
- 5Cystic and papillary neoplasm involving peribiliary glands: a biliary counterpart of branch-type IPMN? HEPATOLOGY 2012;55:2040-2041., .
- 6Multipotent stem/progenitor cells in human biliary tree give rise to hepatocytes, cholangiocytes, and pancreatic islets. HEPATOLOGY 2011; 54: 2159–2172., , , , , , et al.
- 7Human hepatic stem cell and maturational liver lineage biology. HEPATOLOGY 2011; 53: 1035–1045., , , , , , et al.
Vincenzo Cardinale M.D.*, Guido Carpino M.D., Ph.D., , Lola M. Reid Ph.D§, Eugenio Gaudio X.X., Domenico Alvaro X.X.* ¶, * Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Italy, Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy, Department of Health Sciences, University of Rome “Foro Italico”, Rome, Italy, § Department of Cell and Molecular Physiology, Program in Molecular Biology and Biotechnology, UNC School of Medicine, Chapel Hill, NC, ¶ Eleonora Lorillard Spencer-Cenci Foundation, Rome Italy.