Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer

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Elander, NO; Aughton, K; Ghaneh, P; Neoptolemos, JP; Palmer, DH; Cox, TF; Campbell, F; Costello, E; Halloran, CM; Mackey, JR; ...Date
2018-04-01Source Title
British Journal of CancerPublisher
NATURE PUBLISHING GROUPUniversity of Melbourne Author/s
Tebbutt, NiallAffiliation
Surgery (Austin & Northern Health)Metadata
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Journal ArticleCitations
Elander, 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 Status
Open AccessAbstract
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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