Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer
AuthorElander, NO; Aughton, K; Ghaneh, P; Neoptolemos, JP; Palmer, DH; Cox, TF; Campbell, F; Costello, E; Halloran, CM; Mackey, JR; ...
Source TitleBritish Journal of Cancer
PublisherNATURE PUBLISHING GROUP
University of Melbourne Author/sTebbutt, Niall
AffiliationSurgery (Austin & Northern Health)
Document TypeJournal Article
CitationsElander, N. O., Aughton, K., Ghaneh, P., Neoptolemos, J. P., Palmer, D. H., Cox, T. F., Campbell, F., Costello, E., Halloran, C. M., Mackey, J. R., Scarfe, A. G., Valle, J. W., McDonald, A. C., Carter, R., Tebbutt, N. C., Goldstein, D., Shannon, J., Dervenis, C., Glimelius, B. ,... Greenhalf, W. (2018). Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer. BRITISH JOURNAL OF CANCER, 118 (7), pp.947-954. https://doi.org/10.1038/s41416-018-0004-2.
Access StatusOpen Access
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.
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