Look into Hepatic Progenitor Cell Associated Trait：Histological Heterogeneity of Hepatitis B-Related Combined Hepatocellular-Cholangiocarcinoma

• Published in: Current medical science Vol. 37; no. 6; pp. 873 - 879
• Main Author: 蔡雄;熊俊;胡青钢;赵秋东;吴东;唐礼功;万赤丹;卫立辛
• Format: Journal Article
• Language: English
• Published: Wuhan Huazhong University of Science and Technology 01.12.2017; Department of Hepatobiliary Surgery,Union Hospital Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China%Tumor Immunology and Gene Therapy Center,Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai200438,China%Department of Hepatic Surgery,Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai200438,China%Department of Urology,Wuhan General Hospital of PLA,Wuhan 430070,China
• Subjects: Adult; Aged; alpha-Fetoproteins - genetics; alpha-Fetoproteins - metabolism; Antigens, Tumor-Associated, Carbohydrate - blood; Antigens, Tumor-Associated, Carbohydrate - genetics; Bile Duct Neoplasms - genetics; Bile Duct Neoplasms - pathology; Bile Duct Neoplasms - surgery; Bile Duct Neoplasms - virology; Bile Ducts, Intrahepatic - pathology; Bile Ducts, Intrahepatic - surgery; Bile Ducts, Intrahepatic - virology; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - surgery; Carcinoma, Hepatocellular - virology; Cell Dedifferentiation; Cholangiocarcinoma - genetics; Cholangiocarcinoma - pathology; Cholangiocarcinoma - surgery; Cholangiocarcinoma - virology; Female; Hepatitis B - genetics; Hepatitis B - pathology; Hepatitis B - surgery; Hepatitis B - virology; Hepatocytes - pathology; Hepatocytes - virology; Humans; Immunohistochemistry; Keratin-7 - genetics; Keratin-7 - metabolism; Liver - pathology; Liver - surgery; Liver - virology; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Liver Neoplasms - surgery; Liver Neoplasms - virology; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplastic Stem Cells - pathology; Neoplastic Stem Cells - virology; Phenotype; Retrospective Studies; progenitor; histology; human; heterogeneity; cholangiohepatoma
• ISSN: 1672-0733; 2096-5230; 1993-1352; 1993-1352; 2523-899X
• DOI: 10.1007/s11596-017-1820-y

Combined hepatocellular-cholangiocarcinoma（CHC） is a mixed tumor containing elements of both hepatocellular carcinoma（HCC） and cholangiocarcinoma（CC）. Its remarkable histological heterogeneity has been linked to putative hepatic progenitor cell（HPC） origin. However, detailed histological or phenotypic description is rarely documented. In the present study, we reassessed 68 cases previously diagnosed as hepatitis B-related CHCs by immunohistochemistry and double-fluorescence immunostaining, focusing on HPC associated phenotypic observation of intermediate area of the tumor. It was found that tumor cells showed remarkable heterogeneity in intermediate area. Tumor cells with intermediate morphology between hepatocytes and cholangiocytes were oval-shaped and small with scant cytoplasm and hyperchromatic nuclei, arranging in solid nests mostly. By Keratin 7（K7） staining, it appeared that the nests of tumor cells represented a maturation process from the undifferentiated small cells to mature hepatocytes through the ＂transitional＂ cells. Then, these small cells were further confirmed with intermediate phenotype as HPC by exploring immature hepatocellular marker and HPC/biliary markers co-localization. In conclusion, the HPC associated trait in CHC can be interpreted by HPC origin or gain of ＂stemness＂ by dedifferentiation. It is still too soon to give a final word that it is innate or acquired signature of HPC associated trait in CHC.