Combined analyses of hENT1, TS, and DPD predict outcomes of borderline-resectable pancreatic cancer

Abstract

Background: Predicting chemosensitivity to neoadjuvant chemoradiotherapy (NACRT) in pancreatic cancer is desired. The present study aimed to examine the relationship between intratumoral expression of human equilibrative nucleoside transporter 1 (hENT1), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) and the outcomes of NACRT with gemcitabine (GEM) combined with S-1 in patients with borderline-resectable pancreatic cancer (BRPC). Materials and Methods: Forty-seven patients who underwent NACRT with GEM plus S-1, following curative surgery, were recruited in our Institution between 2009 and 2012. Immunohistochemical expressions of hENT1, TS, and DPD in fine-needle aspiration (FNA) biopsies and resected specimens were examined. The correlation between these enzyme expressions and long-term outcome was analyzed. Results: In 21 FNA specimens, no relationship between clinical responses to NACRT and long-term survival was found. However, in 47 resected specimens, patients were classified according to the number of favorable hENT1, TS, and DPD expression factors (hENT1 positive/TS negative/DPD negative). The presence of three favorable factors was strongly associated with improved partial response rates to NACRT (p=0.002). Patients with 2 or more favorable factors showed a significantly longer overall survival than the other patients (p=0.002). Conclusion: Combined expression analyses of hENT1, TS, and DPD may predict long-term outcomes in patients with BRPC after NACRT.