A new immunohistochemistry prognostic score (IPS) for recurrence and survival in resected pancreatic neuroendocrine tumors (PanNET)

Antonio Viúdez; Filipe L F Carvalho; Zahra Maleki; Marianna Zahurak; Daniel Laheru; Alejandro Stark; Nilofer S Azad; Christopher L Wolfgang; Stephen Baylin; James G Herman; Ana De Jesus-Acosta

doi:10.18632/oncotarget.7436

A new immunohistochemistry prognostic score (IPS) for recurrence and survival in resected pancreatic neuroendocrine tumors (PanNET)

Oncotarget. 2016 May 3;7(18):24950-61. doi: 10.18632/oncotarget.7436.

Affiliations

¹ Department of Medical Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
² Department of Medical Oncology, Complejo Hospitalario de Navarra-Instituto de Investigaciones Sanitarias de Navarra-IDISNA, Pamplona, Navarra, Spain.
³ Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
⁴ The Division of Biostatistics and Bioinformatics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

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.

Keywords: MGMT; NDRG-1; PHLDA-3; Pathology Section; immunohistochemistry; pancreatic neuroendocrine tumor.

MeSH terms

Biomarkers, Tumor / analysis*
Cell Cycle Proteins / analysis
Cell Cycle Proteins / biosynthesis
Cell Cycle Proteins / genetics
DNA Methylation
DNA Modification Methylases / analysis
DNA Modification Methylases / biosynthesis
DNA Modification Methylases / genetics
DNA Repair Enzymes / analysis
DNA Repair Enzymes / biosynthesis
DNA Repair Enzymes / genetics
Disease-Free Survival
Female
Humans
Immunohistochemistry / methods
Intracellular Signaling Peptides and Proteins / analysis
Intracellular Signaling Peptides and Proteins / biosynthesis
Intracellular Signaling Peptides and Proteins / genetics
Kaplan-Meier Estimate
Male
Middle Aged
Neoplasm Recurrence, Local / mortality
Neoplasm Recurrence, Local / pathology*
Neuroendocrine Tumors / mortality
Neuroendocrine Tumors / pathology*
Nuclear Proteins / analysis
Nuclear Proteins / biosynthesis
Nuclear Proteins / genetics
Pancreatic Neoplasms / mortality
Pancreatic Neoplasms / pathology*
Prognosis
Tumor Suppressor Proteins / analysis
Tumor Suppressor Proteins / biosynthesis
Tumor Suppressor Proteins / genetics

Substances

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