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TLR-4 expression and decrease in chronic inflammation: indicators of aggressive follicular thyroid carcinoma
  1. Jaana Hagström1,2,
  2. Annukka Heikkilä1,
  3. Päivi Siironen3,
  4. Johanna Louhimo3,
  5. Ilkka Heiskanen3,
  6. Hanna Mäenpää4,
  7. Johanna Arola1,
  8. Caj Haglund1,3
  1. 1Department of Pathology, Haartman Institute, University of Helsinki and HUSLAB, Helsinki, Finland
  2. 2Department of Oral Pathology, University of Helsinki, Helsinki, Finland
  3. 3Department of Surgery, Helsinki University Central Hospital, HUS, Helsinki, Finland
  4. 4Department of Oncology, Helsinki University Central Hospital, HUS, Helsinki, Finland
  1. Correspondence to Dr Jaana Hagström, Department of Pathology, Haartman Institute, P.O. Box 21, 00014 University of Helsinki, HUS, Helsinki, Finland; jaana.hagstrom{at}


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.

Aims 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.

  • Follicular thyroid tumour
  • inflammation
  • metastases
  • oxyphilia
  • immunohistochemistry
  • endocrine pathology
  • thyroid cancer
  • thyroid
  • carcinoma
  • tumour markers
  • cancer research

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  • JH and AH share first authorship.

  • JA and CH contributed equally.

  • Funding This study was funded by the Sigrid Juselius Foundation, Finska Läkaresällskapet, Medicinska understödsföreningen Liv och Hälsa and the Finnish Cancer Foundation.

  • Competing interests None.

  • Ethics approval This study was approved by the Surgical Ethics Committee and National Supervisory Authority for Welfare and Health (Valvira).

  • Provenance and peer review Not commissioned; externally peer reviewed.