title: Toll-like receptors 3, 4 and 9 in hepatocellular carcinoma: Relationship with clinicopathological characteristics and prognosis.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is in the 10 leading cancer types, being difficult to detect as most of patients who develop this tumor have no symptoms other than those related to their long-standing liver disease. The liver is constantly exposed to bacterial products, viral infection, alcohol or other products, which may be the cause of chronic liver damage, and thus an increasing risk for HCC. Toll-like receptors (TLR) have gained an extraordinary interest in cancer research due to their role in several biological processes such as innate immune responses, the induction of adaptive immune responses, regulation of inflammation, would healing and carcinogenesis. Therefore, the aim of this study was to investigate the expression and clinical relevance of TLR3, 4 and 9 in HCC.
  
  
  METHODS
  The expression levels of TLR3, TLR4 and TLR9 were analyzed in tumors from 30 patients with HCC. The analysis was performed by immunohistochemistry. Results were correlated with various clinicopathological findings and with overall survival.
  
  
  RESULTS
  TLR3 was significantly high in large tumors (>4 cm in diameter) compared with small tumors (P < 0.05). Our results demonstrated that patients whose tumors showed both TLR4 and TLR9 positive immunostaining had poor prognosis. In addition, TLR9 expression by fibroblast-like cells was significantly associated with a shortened overall survival (P = 0.015).
  
  
  CONCLUSIONS
  The results demonstrated an association between TLR3, TLR4 and TLR9 expression and tumor aggressiveness and poor prognosis in HCC.
authors.affiliation: Research Unit, Foundation Hospital of Jove, Gijón, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Eiró
authors.forename: Antonio
authors.initials: A
authors.lastname: Altadill
authors.forename: Luis M
authors.initials: LM
authors.lastname: Juárez
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodríguez
authors.forename: Luis O
authors.initials: LO
authors.lastname: González
authors.forename: Sara
authors.initials: S
authors.lastname: Atienza
authors.forename: Sandra
authors.initials: S
authors.lastname: Bermúdez
authors.forename: Belen
authors.initials: B
authors.lastname: Fernandez-Garcia
authors.forename: Manuel F
authors.initials: MF
authors.lastname: Fresno-Forcelledo
authors.forename: Luis
authors.initials: L
authors.lastname: Rodrigo
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Vizoso
keywords: Toll-like receptors; hepatocellular carcinoma; immunology of cancer; overall survival; stromal cells; tumor aggressiveness