Toll-like receptors 1 –9 in small bowel neuroendocrine tumors–Clinical significance and prognosis

by Niko Hiltunen, Niko Kemi, Juha P. V äyrynen, Jan Böhm, Joonas H. Kauppila, Heikki Huhta, Olli Helminen Toll-like receptors (TLRs) are pattern recognition receptors of the innate immunity. TLRs are known to mediate both antitumor effects and tumorigenesis. TLRs are abundant in many cancers, but their expression in small bowel neuroendocrine tumors (SB-NETs) is unknown. We aimed to characterize the e xpression of TLRs 1–9 in SB-NETs and lymph node metastases and evaluate their prognostic relevance. The present study included 125 patients with SB-NETs, of whom 95 had lymph node metastases, from two Finnish hospitals. Tissue samples were stained immunohistochemically for TLR expression, assessed based on cytoplasmic and nucleic staining intensity and percentage of positively stained cells. Statistical methods for survival analysis included Kaplan-Meier method and Cox regression adjusted for confounding factors. Disease-specific survival (DSS) was the primary outcome. TLRs 1–2 and 4–9 w ere expressed in SB-NETs and lymph node metastases. TLR3 showed no positive staining. In primary SB-NETs, TLRs 1–9 were not associated with survival. For lymph node metastases, high cytoplasmic TLR7 intensity associated with worse DSS compared to low cytoplasmic intensity (26.4% vs. 84.9%, p = 0.0 28). Adjusted mortality hazard (HR) was 3.90 (95% CI 1.07–14.3). The expression of TLRs 1–6 and 8–9 in lymph node metastases were not associated with survival. SB-NETs and their lymph ...
Source: PLoS One - Category: Biomedical Science Authors: Source Type: research