title: A fibrous stromal component in hepatocellular carcinoma reveals a cholangiocarcinoma-like gene expression trait and epithelial-mesenchymal transition.
abstract: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major primary liver cancers in adults. The phenotypic overlap between HCC and CC has been shown to comprise a continuous liver cancer spectrum. As a proof of this concept, a recent study demonstrated a genomic subtype of HCC that expressed CC-like gene expression traits, such as CC-like HCC, which revealed the common genomic trait of stem-cell-like properties and aggressive clinical outcomes. Scirrhous HCC (S-HCC), a rare variant of HCC, is characterized by abundant fibrous stroma and has been known to express several liver stem/progenitor cell markers. This suggests that S-HCC may harbor common intermediate traits between HCC and CC, including stem-cell traits, which are similar to those of CC-like HCC. However, the molecular and pathological characteristics of S-HCC have not been fully evaluated. By performing gene-expression profiling and immunohistochemical evaluation, we compared the morphological and molecular features of S-HCC with those of CC and HCC. S-HCC expresses both CC-like and stem-cell-like genomic traits. In addition, we observed the expression of core epithelial-mesenchymal transition (EMT)-related genes, which may contribute to the aggressive behavior of S-HCC. Overexpression of transforming growth factor beta (TGF-β) signaling was also found, implying its regulatory role in the pathobiology of S-HCC.
  
  
  CONCLUSIONS
  We suggest that the fibrous stromal component in HCC may contribute to the acquisition of CC-like gene-expression traits in HCC. The expression of stem-cell-like traits and TGF-β/EMT molecules may play a pivotal role in the aggressive phenotyping of S-HCC. (HEPATOLOGY 2012;55:1776-1786).
authors.affiliation: Department of Pathology, Brain Korea 21 Project for Medical Science, Center for Chronic Metabolic Disease, Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jae Yeon
authors.initials: JY
authors.lastname: Seok
authors.forename: Deuk Chae
authors.initials: DC
authors.lastname: Na
authors.forename: Hyun Goo
authors.initials: HG
authors.lastname: Woo
authors.forename: Massimo
authors.initials: M
authors.lastname: Roncalli
authors.forename: So Mee
authors.initials: SM
authors.lastname: Kwon
authors.forename: Jeong Eun
authors.initials: JE
authors.lastname: Yoo
authors.forename: Ei Yong
authors.initials: EY
authors.lastname: Ahn
authors.forename: Gwang Il
authors.initials: GI
authors.lastname: Kim
authors.forename: Jin-Sub
authors.initials: JS
authors.lastname: Choi
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Kim
authors.forename: Young Nyun
authors.initials: YN
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology*; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005355:Fibrosis; D020869:Gene Expression Profiling; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D016212:Transforming Growth Factor beta