Peritumoral activated hepatic stellate cells predict poor clinical outcome in hepatocellular carcinoma after curative resection

Am J Clin Pathol. 2009 Apr;131(4):498-510. doi: 10.1309/AJCP86PPBNGOHNNL.


The inflammatory components of the liver remnant after hepatocellular carcinoma (HCC) resection are of prognostic importance. We evaluated prognostic potential of peritumoral activated hepatic stellate cells (HSCs) in 130 HCC cases. The messenger RNA (mRNA) levels of the functional genes in HSCs (ie, seprase, osteonectin, and tenascin-C), quantitated by real-time quantitative polymerase chain reaction, and the density of peritumoral Foxp3+ T-regulatory cells (Tregs) and CD68+ macrophages (MPhi), assessed immunohistochemically in tissue microarray sections, were positively correlated with the density of peritumoral activated HSCs. The density (P= .007 for recurrence-free survival [RFS] and P=.021 for overall survival [OS]) and functional genes (seprase, P= .001 for RFS; osteonectin, P= .007 for RFS and P=.021 for OS) of peritumoral activated HSCs independently contributed to high recurrence or death rates, as did peritumoral Tregs or MPhi. Moreover, peritumoral HSCs were related to more early recurrences. It is important to note that the density of peritumoral activated HSCs, in combination with seprase and osteonectin mRNA or density of Tregs and MPhi, might predict prognoses more effectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Neoplasm / biosynthesis
  • Biomarkers, Tumor / biosynthesis
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Female
  • Gelatinases
  • Gene Expression
  • Hepatectomy*
  • Hepatic Stellate Cells / pathology*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Liver Neoplasms / immunology
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Macrophages / immunology
  • Male
  • Membrane Proteins
  • Middle Aged
  • Osteonectin / biosynthesis
  • Prognosis
  • RNA, Messenger / analysis
  • ROC Curve
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serine Endopeptidases / biosynthesis
  • T-Lymphocytes, Regulatory / immunology
  • Tissue Array Analysis
  • Treatment Outcome


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Membrane Proteins
  • Osteonectin
  • RNA, Messenger
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • Gelatinases