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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-03-08

AUTHORS

N. O. Elander, K. Aughton, P. Ghaneh, J. P. Neoptolemos, D. H. Palmer, T. F. Cox, F. Campbell, E. Costello, C. M. Halloran, J. R. Mackey, A. G Scarfe, J. W. Valle, A. C. McDonald, R. Carter, N. C. Tebbutt, D. Goldstein, J. Shannon, C. Dervenis, B. Glimelius, M. Deakin, R. M. Charnley, Alan Anthoney, M. M. Lerch, J. Mayerle, A. Oláh, M. W. Büchler, W. Greenhalf, for the European Study Group for Pancreatic Cancer

ABSTRACT

ABSTRACTBackgroundDihydropyrimidine 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.MethodsDPD 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).ResultsDPD 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).ConclusionDPD 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. More... »

PAGES

947-954

Journal

TITLE

British Journal of Cancer

ISSUE

7

VOLUME

118

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41416-018-0004-2

DOI

http://dx.doi.org/10.1038/s41416-018-0004-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1101377118

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29515256


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