Predictive value of hENT1 immunohistochemistry for gemcitabine-treated pancreatic cancer is antibody dependent.

Abstract

e15746 Background: Pancreatic cancer (PC) continues to have poor outcomes, and biomarkers to guide individualized therapy are needed. Gemcitabine (GEM), a pyrimidine nucleoside, requires plasma membrane transporter proteins to enter cells, and deficiency of the human equilibrative nucleoside transporter 1 (hENT1) protein confers high-level GEM resistance in pre-clinical models. Furthermore, abundance of hENT in PC cells, as determined by immunohistochemistry (IHC), has been variably reported to be associated with improved survival in people with PC treated with GEM. The antibodies (Abs) used for IHC differ in targeted epitope, method of generation, and species of origin. The purpose of this review is to evaluate the contribution of anti-hENT1 Ab choice in finding a link between hENT1 expression and outcomes. Methods: We reviewed the published literature investigating relationships between hENT1 IHC tumor expression and survival in people with PC treated with GEM. Results: Eighteen studies were identified, using five distinct Abs (Table 1). We identified apparent differences in predictive value among Abs (Chi square test p = 0.065). All seven studies using the 10D7G2 Ab reported that high hENT1 expression is associated with significantly better outcomes in GEM-treated patients. Studies that used other anti-hENT1 Abs, in particular SP120 and 11337-1-AP, had lower rates of success. Pooled HRs and additional metrics will be presented. Conclusions: There is significant heterogeneity among studies evaluating the link between hENT1 expression and outcomes. hENT1 IHC with the 10D7G2 Ab is a strong and reproducible predictive marker for improved survival in people with PC treated with GEM. [Table: see text]