Abstract
Pancreatic neuroendocrine tumor (PanNET) is a neoplastic entity in which few prognostic factors are well-known. Here, we aimed to evaluate the prognostic significance of N-myc downstream-regulated gen-1 (NDRG-1), O6-methylguanine DNA methyltransferase (MGMT) and Pleckstrin homology-like domain family A member 3 (PHLDA-3) by immunohistochemistry (IHC) and methylation analysis in 92 patients with resected PanNET and follow-up longer than 24 months. In multivariate analyses, ki-67 and our immunohistochemistry prognostic score (IPS-based on MGMT, NDRG-1 and PHLDA-3 IHC expression) were independent prognostic factors for disease-free-survival (DFS), while age and IPS were independent prognostic factors for overall survival (OS). Our IPS could be a useful prognostic biomarker for recurrence and survival in patients following resection for PanNET.
Highlights
Pancreatic neuroendocrine tumor (PanNET) represents up to 5% of all pancreatic tumors [1,2,3,4]
No significant associations were observed between N-myc downstream-regulated gen-1 (NDRG-1) pattern and methylguanine DNA methyltransferase (MGMT) IHC, ki-67 or Pleckstrin homology-like domain family A member 3 (PHLDA-3) score
We have described the prevalence and prognostic implications of MGMT, NDRG-1 and PHLDA-3 by IHC and methylation in patients with resected PanNET
Summary
Pancreatic neuroendocrine tumor (PanNET) represents up to 5% of all pancreatic tumors [1,2,3,4]. Most patients have an indolent clinical course, some patients have a more aggressive disease resistant to most available treatments [5]. The World Health Organization (WHO) and the European Neuroendocrine Tumor Society (ENETS) have established prognostic-oriented criteria based on pathological specimens [9,10]. Higher tumor grade and high proliferative index Ki-67 have been associated with a more aggressive clinical course. These pathological criteria help to determine therapeutic decisions in patients with unresectable or metastatic disease [11]. There is an unmet need for prognostic biomarkers that can stratify patients at high risk for recurrence after surgical resection and/or to select the best treatment from available options
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