NAMPT expression in stage I/II pancreatic ductal adenocarcinoma.

Abstract

e15735 Background: NAD (nicotinamide adenine dinucleotide), a vital cofactor in redox reactions and a substrate for many enzymes, plays a critical role in cellular metabolism. NAMPT (nicotinamide phosphoribosyltransferase) is a key enzyme that regenerates NAD from its metabolites. NAMPT has been shown to be overexpressed in some cancers, and inhibition of NAMPT in pancreas cancer cell lines and xenografts has been shown to decrease cell growth, making it an attractive potential therapeutic target. Here we correlate NAMPT expression in a large cohort of stage I/II pancreatic ductal adenocarcinomas (PDA) with clinical outcomes and pathologic features. Methods: NAMPT immunohistochemistry (IHC) was performed on tissue microarrays of 250 PDAs. Tumors had been arrayed in triplicate. Each core was evaluated for staining intensity of cancer cells (0 = no staining, 1+ = weak, 2+ = moderate, 3+ = strong), and a mean score was calculated for each case; cases with fewer than 2 cores were excluded. Fisher’s exact and Wilcoxon rank sum tests were used for categorical and continuous variables, respectively. Recurrence-free survival (RFS) and overall survival (OS) differences were evaluated using Cox regression. This study was conducted under an approved IRB protocol. Results: 197 PDAs had at least 2 TMA cores with identifiable cancer cells. The mean IHC score was 0.53 (range 0 to 2.33). While 121/197 PDAs (61%) were positive, only 18/197 (9%) had a score > 1. Stage II tumors had a higher mean score than stage I tumors (0.57 vs 0.31; P = 0.03) and were more likely to be positive (66% of 148 vs 41% of 22; P = 0.03). However, RFS and OS were not significantly different between NAMPT-positive vs NAMPT-negative PDAs. Conclusions: NAMPT expression was detected in 61% of stage I/II PDAs. Frequency and extent of expression correlated with overall stage, suggesting a role in cancer progression. Although NAMPT expression did not correlate with RFS and OS in this study, given its frequent expression in PDA, it represents a potential therapeutic target.