Expression of gremlin 1 correlates with increased angiogenesis and progression-free survival in patients with pancreatic neuroendocrine tumors

J Gastroenterol. 2013 Jan;48(1):101-8. doi: 10.1007/s00535-012-0614-z. Epub 2012 Jun 16.

Abstract

Background: Gremlin 1 (GREM1) is a bone morphogenetic protein antagonist and a novel proangiogenic factor. Our aim was to evaluate the prognostic value of GREM1 expression and GREM1-related factors in tumor-associated angiogenesis in pancreatic neuroendocrine tumors (NETs).

Methods: The immunohistochemical expression of GREM1 and microvessel density (MVD) were examined in 35 patients with pancreatic NETs and then compared with other clinicopathologic characteristics, including the World Health Organization classification.

Results: The presence of expression of GREM1 (p = 0.016) and high MVD (p = 0.020) were significant and favorable prognostic factors. Moreover, GREM1 expression was significantly associated with high MVD (p = 0.011). MVD was significantly higher in well-differentiated NETs than in well-differentiated or poorly differentiated neuroendocrine carcinomas (p < 0.001).

Conclusions: GREM1 expression was correlated with tumor-associated angiogenesis and was found to be a novel prognostic marker in pancreatic NETS. Our data support a tumor suppressor role of GREM1 in pancreatic NETs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Kaplan-Meier Estimate
  • Male
  • Microvessels / pathology
  • Middle Aged
  • Neovascularization, Pathologic / metabolism*
  • Neuroendocrine Tumors / blood supply*
  • Neuroendocrine Tumors / metabolism*
  • Neuroendocrine Tumors / pathology
  • Neuroendocrine Tumors / surgery
  • Pancreatic Neoplasms / blood supply*
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery
  • Young Adult

Substances

  • Biomarkers, Tumor
  • GREM1 protein, human
  • Intercellular Signaling Peptides and Proteins