The prognostic role of tissue TLR2 and TLR4 in colorectal cancer
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ORIGINAL ARTICLE
The prognostic role of tissue TLR2 and TLR4 in colorectal cancer Ines Beilmann-Lehtonen 1 Caj Haglund 1,2,3
&
Camilla Böckelman 1,2 & Harri Mustonen 1 & Selja Koskensalo 1 & Jaana Hagström 3 &
Received: 2 October 2019 / Revised: 17 April 2020 / Accepted: 28 April 2020 # The Author(s) 2020
Abstract Colorectal cancer (CRC), the second most common cancer globally, resulted in 881,000 deaths in 2018. Toll-like receptors (TLRs) are crucial to detecting pathogen invasion and inducing the host’s immune response. This study aimed to explore the prognostic value of TLR2 and TLR4 tumor expressions in colorectal cancer patients. We studied the immunohistochemical expressions of TLR2 and TLR4 using tissue microarray specimens from 825 patients undergoing surgery in the Department of Surgery, Helsinki University Hospital, between 1982 and 2002. We assessed the relationships between TLR2 and TLR4 expressions and clinicopathological variables and patient survival. We generated survival curves using the Kaplan-Meier method, determining significance with the log-rank test. Among patients with lymph node–positive disease and no distant metastases (Dukes C), a strong TLR2 immunoactivity associated with a better prognosis (p < 0.001). Among patients with local Dukes B disease, a strong TLR4 immunoactivity associated with a worse disease-specific survival (DSS; p = 0.017). In the multivariate survival analysis, moderate TLR4 immunoactivity compared with strong TLR4 immunoactivity (hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.49–0.89, p = 0.007) served as an independent prognostic factor. In the multivariate analysis for the Dukes subgroups, moderate TLR2 immunoactivity (HR 2.63, 95% CI 1.56–4.44, p < 0.001) compared with strong TLR2 immunoactivity served as an independent negative prognostic factor in the Dukes C subgroup. TLR2 and TLR4 might be new prognostic factors to indicate which CRC patients require adjuvant therapy and which could spare from an unnecessary followup, but further investigations are needed. Keywords Toll-like receptor 2 . Toll-like receptor 4 . Colorectal cancer . Colon cancer . Immunohistochemistry
Abbreviations TLR Toll-like receptor TLR2 Toll-like receptor 2 TLR4 Toll-like receptor 4 CRC Colorectal cancer
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00428-020-02833-5) contains supplementary material, which is available to authorized users. * Ines Beilmann-Lehtonen [email protected] 1
Department of Surgery, University of Helsinki and Helsinki University Hospital HUS, Haartmaninkatu 4, PO Box 440, FIN-00029 Helsinki, Finland
2
Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
3
Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
CI HR IQR TMA CRP TME SIR DSS DC MyD88 IBD NF- B
Confidence interval Hazard ratio Interquartile range Tissue microarray C-reactive protein Tumor microenvironment Systemic inflamma
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