title: Intrahepatic cholangiocarcinoma in cirrhosis presents granulocyte and granulocyte-macrophage colony-stimulating factor.
abstract: Intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular and cholangiocarcinoma (HC-CC) are known to arise occasionally in hepatitis-related cirrhosis, although their clinicopathological features remain unclarified. In this study, we characterized the ICC (9 cases) and ICC elements of HC-CC (11 cases) arising in nonbiliary cirrhosis. Thirty-three hepatocellular carcinomas (HCC) associated with nonbiliary cirrhosis and 24 ICC without cirrhosis were used as controls. Prominent neutrophilic infiltration was frequent in ICC with cirrhosis (78%) and ICC elements of combined HC-CC (72%). Neutrophilic infiltration-related cytokines (interleukin 8, granulocyte colony-stimulating factor [G-CSF], and granulocyte macrophage colony-stimulating factor [GM-CSF]) were expressed frequently and intensely in carcinoma cells of ICC with cirrhosis (40%, 80%, and 60%, respectively) and in ICC elements of the combined one (13%, 38%, and 63%, respectively). Interleukin 8 was expressed in 18% of ICC without cirrhosis, irrespective of neutrophilic infiltration. Neutrophilic infiltration and expression of G-CSF and GM-CSF were in parallel (P < 0.05). G-CSF and GM-CSF mRNA were detected by RT-PCR in tissue specimens expressing G-CSF and GM-CSF at the protein level. Such neutrophilic infiltration and expression of G-CSF and GM-CSF were not evident in controls. The expressions of c-kit and c-Met, as a hematopoietic and hepatic stem cell marker, were seen frequently in ICC with cirrhosis (80% and 80%, respectively) and ICC elements of the combined one (63% and 50%, respectively). The present study revealed that the frequent expression of G-CSF and GM-CSF is a characteristic of ICC with cirrhosis and ICC in combined carcinoma, probably representing a phenotype of fetal hepatic parenchymal cell. The expression of these cytokines may be causally related to prominent neutrophilic infiltration.
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Sasaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: Akira
authors.initials: A
authors.lastname: Ishikawa
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology*; D018281:Cholangiocarcinoma / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D010641:Phenotype; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000096:biosynthesis; D013234:Stem Cells / Q000502:physiology
chemical_list: D016209:Interleukin-8; D012333:RNA, Messenger; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019859:Proto-Oncogene Proteins c-met