title: TLR-4 expression and decrease in chronic inflammation: indicators of aggressive follicular thyroid carcinoma.
abstract: BACKGROUND
  Well-differentiated follicular thyroid carcinoma usually has a favourable prognosis and metastases are rare. Toll-like receptors (TLRs) that take part in adaptive and innate immunity have, in many tumours, both apoptotic and antiapoptotic effects, making their role in tumourigenesis controversial. Chronic inflammation is involved in many cancers.
  
  
  OBJECTIVE
  To examine the clinical relevance of TLR-2, TLR-4, and CD45 in follicular thyroid neoplasias.
  
  
  METHODS
  The authors studied the immunohistochemical expression of TLR-2 and TLR-4 in 127 follicular thyroid neoplasms, both in adenomas and in carcinomas including oxyphilic tumours. Their degree of chronic inflammation was evaluated by a count of CD45-positive lymphocytes within and adjacent to the tumourous tissue.
  
  
  RESULTS
  Both high TLR-4 expression and lack of TLR-4 expression in carcinomas were associated with metastatic and aggressive disease. In oxyphilic tumours, both in adenomas and in carcinomas, TLR-4 expression was significantly stronger. TLR-2 expression was stronger in adenomas than in carcinomas but without any correlation with clinical variables. Degree of chronic inflammation outside the primary tumour was lower for metastasized carcinomas than for non-metastasised carcinomas.
  
  
  CONCLUSIONS
  Varying expression of TLR-4 and lack of inflammation are indicators of aggressive disease among follicular thyroid cancer.
authors.affiliation: Department of Pathology, Haartman Institute, University of Helsinki and HUSLAB, Helsinki, Finland. jaana.hagstrom@hus.fi
authors.forename: Jaana
authors.initials: J
authors.lastname: Hagström
authors.forename: Annukka
authors.initials: A
authors.lastname: Heikkilä
authors.forename: Päivi
authors.initials: P
authors.lastname: Siironen
authors.forename: Johanna
authors.initials: J
authors.lastname: Louhimo
authors.forename: Ilkka
authors.initials: I
authors.lastname: Heiskanen
authors.forename: Hanna
authors.initials: H
authors.lastname: Mäenpää
authors.forename: Johanna
authors.initials: J
authors.lastname: Arola
authors.forename: Caj
authors.initials: C
authors.lastname: Haglund
mesh_terms: D018263:Adenocarcinoma, Follicular; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D002908:Chronic Disease; D050031:Hashimoto Disease / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D017493:Leukocyte Common Antigens / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology*; D013966:Thyroiditis; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D017493:Leukocyte Common Antigens