Multiple cells of origin in cholangiocarcinoma underlie biological, epidemiological and clinical heterogeneity

Table 1 Phenotype markers of candidate cholangiocarcinoma cells of origin

Marker	Mature cholangiocytes	hHpSCs in canals of Hering	BTSC in peribiliary glands
Nanog, OCT4	-	-	+
CXCR4	-	-	+
FoxA ½	-	-	+
PDX1, NGN3	-	-	+
AFP	-	+	+
Sox 9/17	-	+	+
Prominin-1 (CD133)	-	+	+
EpCAM	+/-	+	+
NCAM	-	+	+
Thy	-	+	+
CK7/19	+	+	+
Secretin Receptor	+	-	-
γGT	+	+/-	+/-

Comparison of the phenotype among mature cholangiocytes, hepatic stem cells (hHpSCs) in canals of hering and biliary tree stem/progenitor cells (BTSC) in peribiliary glands. Mature cholangiocytes do not express markers of stem/progenitor cells. A complete study of the phenotype of cholangiocarcinoma considering these markers would indicate the probable cell of origin. AFP: α-fetoprotein; CD133: Prominin; CK: Cytokeratin; CXCR4: CXC-chemokine receptor 4; EpCAM: Epithelial cell adhesion molecule; FOXa2: Forkhead box a2; γGT: γ-glutamiltranspeptidasi; NCAM: Neural cell adhesion molecule; NGN3: Neurogenin 3; OCT4: Octamer-binding transcription factor 4 also known as POU5F1 (POU domain, class 5, transcription factor 1); PDX1: Pancreatic and duodenal homeobox 1; SOX: Sry-related HMG box.