C-Reactive Protein as a New Prognostic Factor for Survival in Patients With Pancreatic Neuroendocrine Neoplasia

J Clin Endocrinol Metab. 2016 Mar;101(3):937-44. doi: 10.1210/jc.2015-3114. Epub 2015 Dec 17.


Context: Patients with pancreatic neuroendocrine neoplasia (pNEN) show great variability in prognosis and treatment response. Additional prognostic markers might help in individual therapeutic decision making.

Objective: The objective of the study was to investigate the association between preoperative plasma levels of C-reactive protein (CRP) and overall survival (OS) in pNEN.

Design: This was a single-center, retrospective analysis of long-term prospective patient-database.

Setting: The study was conducted at a tertiary referral center.

Patients: All 149 patients with sporadic pNENs were eligible for retrospective analysis.

Main outcome measure: Cumulative overall survival, compared between patients with elevated and normal CRP levels, was measured.

Results: Median OS for patients with elevated CRP levels was 1093 days (SE 1261, 95% confidence interval [CI] 0-3565), compared with 6859 days (SE 1252, 95% CI 4405-9313) for patients with normal CRP levels. Log rank test showed a significant correlation between CRP and OS (P < .001). In univariate Cox regression, patients with elevated CRP levels had a significantly higher hazard ratio for death (3.27; 95%-CI 1.74-6.16; P < .001). This finding persisted after multivariable adjustment. Furthermore, OS was associated with the presence of liver metastases (hazard ratio 3.17; 95% CI 1.88-5.35; P < .001), incomplete resection (R1/R2 status; hazard ratio 3.99; 95% CI 2.16-7.35; P < .001) and Ki-67 percentage (hazard ratio 5.05; 95% CI 2.17-11.76; P < .001).

Conclusion: CRP is an independent prognostic marker in patients with pNEN. Pretreatment CRP measurements should be considered for incorporation into prospective studies of outcome in patients with pNENs and clinical trials of systemic therapies for these tumors.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood*
  • C-Reactive Protein / analysis*
  • Female
  • Humans
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / mortality*
  • Neuroendocrine Tumors / surgery
  • Pancreatic Neoplasms / mortality*
  • Pancreatic Neoplasms / surgery
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Retrospective Studies
  • Survival Rate


  • Biomarkers
  • C-Reactive Protein