title: Tumor progression in hepatocellular carcinoma: relationship with tumor stroma and parenchymal disease.
abstract: BACKGROUND
  Encapsulation in hepatocellular carcinoma is associated with decreased invasiveness and improved survival in several series. Although active fibrogenesis by myofibroblasts has been demonstrated in the capsule, it is unclear if the capsule results from a general increase in peritumoral fibrosis, or an inherently less invasive tumor phenotype. The relationship between collagen deposition within tumor stroma, presence of cirrhosis and invasiveness also needs clarification.
  
  
  METHODS
  We performed immunohistochemistry for collagens I, III, IV and VI on sections of encapsulated and non-encapsulated hepatocellular carcinoma, arising in cirrhotic and non-cirrhotic livers. Staining was graded semi-quantitatively in tumor stromal elements and adjacent parenchymal sinusoids. The relationship of this staining with encapsulation, cirrhosis, and vascular invasion was analyzed.
  
  
  RESULTS
  Formation of a discrete capsular layer was associated with reduced vascular invasion, but not with a pervasive increase in peritumoral fibrosis. Increased collagen I content of tumor stroma and adjacent parenchymal sinusoids was associated with non-encapsulated tumors and vascular invasion. The presence of cirrhosis had little effect on capsule composition.
  
  
  CONCLUSIONS
  Encapsulation of hepatocellular carcinoma reflects reduced invasiveness, rather than increased peritumoral collagen synthesis, which may instead enhance invasion. Increased intratumoral collagen I protein is also associated with increased tumor invasiveness. Pre-existing cirrhosis has little effect on tumor progression, possibly because the characteristics of cirrhosis are overwhelmed by tumor-induced changes in the adjacent parenchyma.
authors.affiliation: Department of Surgery, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: David S R
authors.initials: DS
authors.lastname: Lockwood
authors.forename: Trina M
authors.initials: TM
authors.lastname: Yeadon
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Clouston
authors.forename: Darrell G
authors.initials: DG
authors.lastname: Crawford
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fawcett
authors.forename: Shirley A
authors.initials: SA
authors.lastname: Callaghan
authors.forename: David C
authors.initials: DC
authors.lastname: Gotley
mesh_terms: D001315:Australia; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D024142:Collagen Type VI / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D012307:Risk Factors; D013223:Statistics as Topic; D017154:Stromal Cells / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D024042:Collagen Type I; D024061:Collagen Type III; D024141:Collagen Type IV; D024142:Collagen Type VI