University of Oulu

Paarnio, K., Väyrynen, S., Klintrup, K., Ohtonen, P., Mäkinen, M., Mäkelä, J., Karttunen, T., Divergent expression of bacterial wall sensing toll-like receptors 2 and 4 in colorectal cancer, World Journal of Gastroenterology, Vol. 23:26, p. 4831-4838, ISSN: 1007-9327, DOI: 10.3748/wjg.v23.i26.4831

Divergent expression of bacterial wall sensing toll-like receptors 2 and 4 in colorectal cancer

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Author: Paarnio, Karoliina1,2; Väyrynen, Sara1,3; Klintrup, Kai1,2;
Organizations: 1Oulu University Hospital and Medical Research Center Oulu, POB 21, 90029 Oulu, Finland
2Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu, POB 5000, 90014 Oulu, Finland
3Cancer and Translational Medicine Research Unit, University of Oulu, POB 5000, 90014 Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.6 MB)
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Language: English
Published: Baishideng Publishing Group, 2017
Publish Date: 2019-11-05


Aim: To characterize the expression of toll-like receptors (TLR) 2 and 4 in colorectal cancer (CRC) and in normal colorectal mucosa.

Methods: We analysed tissue samples from a prospective series of 118 unselected surgically treated patients with CRC. Sections from formalin fixed, paraffin embedded specimens were analysed for TLR2 and TLR4 expression by immunohistochemistry. Two independent assessors evaluated separately expression at the normal mucosa, at the invasive front and the bulk of the carcinoma, and in the lymph node metastases when present. Expression levels in different locations were compared and their associations with clinicopathological features including TNM-stage and the grade of the tumour and 5-year follow-up observations were analysed.

Results: Normal colorectal epithelium showed a gradient of expression of both TLR2 and TLR4 with low levels in the crypt bases and high levels in the surface. In CRC, expression of both TLRs was present in all cases and in the major proportion of tumour cells. Compared to normal epithelium, TLR4 expression was significantly weaker but TLR2 expression stronger in carcinoma cells. Weak TLR4 expression in the invasive front was associated with distant metastases and worse cancer-specific survival at 5 years. In tumours of the proximal colon the cancer-specific survival at 5 years was 36.9% better with strong TLR4 expression as compared with those with weak expression (P = 0.044). In contrast, TLR2 expression levels were not associated with prognosis. Tumour cells in the lymph node metastases showed higher TLR4 expression and lower TLR2 expression than cells in primary tumours.

Conclusion: Tumour cells in CRC show downregulation of TLR4 and upregulation of TLR2. Low expression of TLR4 in the invasive front predicts poor prognosis and metastatic disease.

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Series: World journal of gastroenterology
ISSN: 1007-9327
ISSN-E: 2219-2840
ISSN-L: 1007-9327
Volume: 23
Issue: 26
Pages: 4831 - 4838
DOI: 10.3748/wjg.v23.i26.4831
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: Supported by a grant from the Mary and Georg C Ehrnrooth Foundation, Finland.
Copyright information: © The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved. This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: