Usefulness of an immunohistochemical score in advanced pancreatic neuroendocrine tumors treated with CAPTEM or everolimus

Pancreatology. 2021 Jan;21(1):215-223. doi: 10.1016/j.pan.2020.12.009. Epub 2020 Dec 19.

Abstract

Background: Pancreatic neuroendocrine tumors are rare neoplasms for which few predictive and/or prognostic biomarkers have been validated. Our previous work suggested the potential of the combined expression 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) as prognostic factors for relapse and survival.

Methods: In this new multicenter study we evaluated immunohistochemistry expression in 76 patients with advanced PanNET who were treated with capecitabine-temozolomide or everolimus. Based on the immunohistochemistry panel, an immunohistochemistry prognostic score (IPS) was developed.

Results: In patients treated with capecitabine and temozolomide, low IPS was an independent prognostic factor for progression-free-survival and overall-survival. Similar findings were observed with highest IPS for overall-survival in patients treated with everolimus.

Conclusion: From our knowledge, it is the first time that a simple IPS could be useful to predict outcome for patients with metastatic pancreatic neuroendocrine tumors treated with everolimus or capecitabine and temozolomide.

Keywords: Biomarker; Immunohistochemistry; MGMT; Metastatic pancreatic neuroendocrine tumor; NDRG-1; PHLDA-3; Predictive factor; Prognosis factor.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis
  • Cell Cycle Proteins / analysis
  • Cell Line, Tumor
  • DNA Modification Methylases / analysis
  • DNA Repair Enzymes / analysis
  • Everolimus / therapeutic use*
  • Female
  • Humans
  • Immunohistochemistry / methods*
  • Immunosuppressive Agents / therapeutic use*
  • Intracellular Signaling Peptides and Proteins / analysis
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / mortality
  • Neuroendocrine Tumors / pathology*
  • Nuclear Proteins / analysis
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Prognosis
  • Progression-Free Survival
  • Survival Analysis
  • Tumor Suppressor Proteins / analysis
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Immunosuppressive Agents
  • Intracellular Signaling Peptides and Proteins
  • N-myc downstream-regulated gene 1 protein
  • Nuclear Proteins
  • TSSC3 protein
  • Tumor Suppressor Proteins
  • Everolimus
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes