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World J Gastrointest Oncol. May 15, 2012; 4(5): 94-102
Published online May 15, 2012. doi: 10.4251/wjgo.v4.i5.94
Multiple cells of origin in cholangiocarcinoma underlie biological, epidemiological and clinical heterogeneity
Vincenzo Cardinale, Guido Carpino, Lola Reid, Eugenio Gaudio, Domenico Alvaro
Vincenzo Cardinale, Domenico Alvaro, Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, 00137 Rome, Italy
Guido Carpino, Eugenio Gaudio, Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, 000137 Rome, Italy
Guido Carpino, Department of Health Sciences, University of Rome “Foro Italico”, 000135 Rome, Italy
Lola Reid, Department of Cell and Molecular Physiology, Biomedical Engineering, Program in Molecular Biology and Biotechnology, UNC School of Medicine, Chapel Hill, NC 27599, United States
Domenico Alvaro, Eleonora Lorillard Spencer-Cenci Foundation, 00156 Rome, Italy
Author contributions: Cardinale V, Carpino G, Reid L, Gaudio E and Alvaro D provided substantial contributions to the conception and design, drafting the article and revising the final approval of the version to be published.
Supported by Research Project Grant from the University “Sapienza” of Rome and FIRB grant No. RBAP10Z7FS_001, PRIN grant No. 2009X84L84_001 (to Gaudio E); FIRB grant No. RBAP10Z7FS_004, PRIN grant No. 2009X84L84_002 (to Alvaro D); Consorzio Interuniversitario Trapianti d’Organo, Rome, Italy
Correspondence to: Domenico Alvaro, Professor, Division of Gastroenterology, Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Fondazione Eleonora Lorillard Spencer Cenci, Sapienza University of Rome, Viale dell'Universita 37, 00185 Rome, Italy. domenico.alvaro@uniroma1.it
Telephone: +39-64-9972023 Fax: +39-64-453319
Received: September 21, 2011
Revised: January 7, 2012
Accepted: January 15, 2012
Published online: May 15, 2012

Recent histological and molecular characterization of cholangiocarcinoma (CCA) highlights the heterogeneity of this cancer that may emerge at different sites of the biliary tree and with different macroscopic or morphological features. Furthermore, different stem cell niches have been recently described in the liver and biliary tree, suggesting this as the basis of the heterogeneity of intrahepatic (IH)- and extrahepatic (EH)-CCAs, which are two largely different tumors from both biological and epidemiological points of view. The complexity of the organization of the liver stem cell compartments could underlie the CCA clinical-pathological heterogeneity and the criticisms in classifying primitive liver tumors. These recent advances highlight a possible new classification of CCAs based on cells of origin and this responds to the need of generating homogenous diagnostic, prognostic and, hopefully, therapeutic categories of IH- and EH-CCAs.

Keywords: Intrahepatic cholangiocarcinoma, Extrahepatic cholangiocarcinoma, Cholangiocarcinoma classification, Cholangiolocarcinoma, Cells of origin, Cancer stem cells, Peribiliary glands, Biliary tree stem/progenitor cells, Human hepatic stem cells, Risk factors, Targeted therapies