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Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer
Univ Liverpool, Canc Res UK Liverpool Canc Trials Unit, Liverpool, Merseyside, England..
Univ Liverpool, Canc Res UK Liverpool Canc Trials Unit, Liverpool, Merseyside, England..
Univ Liverpool, Canc Res UK Liverpool Canc Trials Unit, Liverpool, Merseyside, England..
Heidelberg Univ, Dept Surg, Heidelberg, Germany..
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2018 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 118, no 7, p. 947-954Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2018. Vol. 118, no 7, p. 947-954
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-351639DOI: 10.1038/s41416-018-0004-2ISI: 000429279300004PubMedID: 29515256OAI: oai:DiVA.org:uu-351639DiVA, id: diva2:1211627
Available from: 2018-05-31 Created: 2018-05-31 Last updated: 2018-05-31Bibliographically approved

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