Impact of CRP in pNENs. (A and B) Immunohistochemical and (C) Western blot analysis showing high CRP and IL-6 expression in tumor sections of patients with high pre-operative serum CRP concentrations (≥5 mg/L) in comparison to patients with low pre-operative serum CRP concentrations (<5 mg/L). There were no correlations between grading (3 NET G1, 8 NET G2 and 3 G3) and CRP. (C and D) High pre-operative serum CRP concentrations (≥5 mg/L) lead to significant phosphorylation of STAT3, ERK and AKT, as well as strongly increased IL-6 expression in tumor tissue in comparison to low pre-operative serum CRP concentrations (Western blot, *P < 0.05), thereby supporting CRP exposure to be relevant for neuroendocrine tumor cells with regards to proliferation and tumor biology. (E) Both IL-6 and G-CSF were significantly increased in serum from pNENs patients with high pre-operative serum CRP concentration (≥5 mg/L) (ELISA, *P < 0.05). NML, normal pancreas tissue; pNEN-L, pNEN patients with low pre-operative serum CRP concentrations; pNEN-H: pNEN patients with high pre-operative serum CRP concentrations.