Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/17919
Title: Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer.
Authors: 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, Niall C;Goldstein, D;Shannon, J;Dervenis, C;Glimelius, B;Deakin, M;Charnley, R M;Anthoney, Alan;Lerch, M M;Mayerle, J;Oláh, A;Büchler, M W;Greenhalf, W
Affiliation: From the Cancer Research U.K. Liverpool Cancer Trials Unit, University of Liverpool, Liverpool, UK
Cross Cancer Institute and University of Alberta, Alberta, Canada
University of Manchester/The Christie NHS Foundation Trust, Manchester, UK
The Beatson West of Scotland Cancer Centre, Glasgow, Scotland, UK
Glasgow Royal Infirmary, Glasgow, Scotland, UK
Austin Health, Heidelberg, Victoria, Australia
Prince of Wales hospital and Clinical School University of New South Wales, New South Wales, Australia
Nepean Cancer Centre and University of Sydney, Sydney, Australia
The Agia Olga Hospital, Athens, Greece
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
University Hospital, North Staffordshire, UK
Freeman Hospital, Newcastle upon Tyne, UK
St James's University Hospital, Leeds, UK
Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
Department of Medicine II, University Hospital of the Ludwig-Maximilians-University, Munich, Germany
The Petz Aladar Hospital, Gyor, Hungar
The Department of Surgery, University of Heidelberg, Heidelberg, Germany
Issue Date: Apr-2018
EDate: 2018-03-08
Citation: British journal of cancer 2018; 118(7): 947-954
Abstract: 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. 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). 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). 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/17919
DOI: 10.1038/s41416-018-0004-2
PubMed URL: 29515256
Type: Journal Article
Appears in Collections:Journal articles

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