TY - JOUR AU - Elander, NO AU - Aughton, K AU - Ghaneh, P AU - Neoptolemos, JP AU - Palmer, DH AU - Cox, TF AU - Campbell, F AU - Costello, E AU - Halloran, CM AU - Mackey, JR AU - Scarfe, AG AU - Valle, JW AU - McDonald, AC AU - Carter, R AU - Tebbutt, NC AU - Goldstein, D AU - Shannon, J AU - Dervenis, C AU - Glimelius, B AU - Deakin, M AU - Charnley, RM AU - Anthoney, A AU - Lerch, MM AU - Mayerle, J AU - Olah, A AU - Buechler, MW AU - Greenhalf, W Y2 - 2020/12/18 Y1 - 2018/04/01 SN - 0007-0920 UR - http://hdl.handle.net/11343/256164 AB - BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy. METHODS: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA). RESULTS: DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.73 [95% confidence interval, CI = 1.21-2.49], p = 0.003). This was significant in the 5FU/FA arm (HR = 2.07 [95% CI = 1.22-3.53], p = 0.007), but not in the gemcitabine arm (HR = 1.47 [0.91-3.37], p = 0.119). High hENT1 tumour expression was associated with increased survival in gemcitabine treated (HR = 0.56 [0.38-0.82], p = 0.003) but not in 5FU/FA treated patients (HR = 1.19 [0.80-1.78], p = 0.390). In patients with low hENT1 tumour expression, high DPD tumour expression was associated with a worse median [95% CI] survival in the 5FU/FA arm (9.7 [5.3-30.4] vs 29.2 [19.5-41.9] months, p = 0.002) but not in the gemcitabine arm (14.0 [9.1-15.7] vs. 18.0 [7.6-15.3] months, p = 1.000). The interaction of treatment arm and DPD expression was not significant (p = 0.303), but the interaction of treatment arm and hENT1 expression was (p = 0.009). CONCLUSION: DPD tumour expression was a negative prognostic biomarker. Together with tumour expression of hENT1, DPD tumour expression defined patient subgroups that might benefit from either postoperative 5FU/FA or gemcitabine. LA - English PB - NATURE PUBLISHING GROUP T1 - Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer DO - 10.1038/s41416-018-0004-2 IS - British Journal of Cancer VL - 118 IS - 7 SP - 947-954 L1 - /bitstream/handle/11343/256164/PMC5931115.pdf?sequence=1&isAllowed=y ER -