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Observational Study
. 2018 Apr;118(8):1084-1088.
doi: 10.1038/s41416-018-0005-1. Epub 2018 Mar 9.

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy

N O Elander  1 , K Aughton  1 , P Ghaneh  1 , J P Neoptolemos  1 , D H Palmer  1 , T F Cox  1 , F Campbell  1 , E Costello  1 , C M Halloran  1 , J R Mackey  2 , A G Scarfe  2 , J W Valle  3 , A C McDonald  4 , R Carter  5 , N C Tebbutt  6 , D Goldstein  7 , J Shannon  8 , C Dervenis  9 , B Glimelius  10 , M Deakin  11 , R M Charnley  12 , A Anthoney  13 , M M Lerch  14 , J Mayerle  15 , A Oláh  16 , M W Büchler  17 , W Greenhalf  18 ; European Study Group for Pancreatic Cancer
Affiliations
Observational Study

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy

N O Elander et al. Br J Cancer. 2018 Apr.

Abstract

Background: Deoxycytidylate deaminase (DCTD) and ribonucleotide reductase subunit M1 (RRM1) are potential prognostic and predictive biomarkers for pyrimidine-based chemotherapy in pancreatic adenocarcinoma.

Methods: Immunohistochemical staining of DCTD and RRM1 was performed on tissue microarrays representing tumour samples from 303 patients in European Study Group for Pancreatic Cancer (ESPAC)-randomised adjuvant trials following pancreatic resection, 272 of whom had received gemcitabine or 5-fluorouracil with folinic acid in ESPAC-3(v2), and 31 patients from the combined ESPAC-3(v1) and ESPAC-1 post-operative pure observational groups.

Results: Neither log-rank testing on dichotomised strata or Cox proportional hazard regression showed any relationship of DCTD or RRM1 expression levels to survival overall or by treatment group.

Conclusions: Expression of either DCTD or RRM1 was not prognostic or predictive in patients with pancreatic adenocarcinoma who had had post-operative chemotherapy with either gemcitabine or 5-fluorouracil with folinic acid.

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Conflict of interest statement

J.P.N. reports a consulting or advisory role for Boehringer Ingelheim Pharma GmbH & Co. KG; Novartis Pharma AG; KAEL GemVax and Astellas. Research Funding from Taiho Pharma (Japan), PI, paid to Institution; KAEL GemVax (Korea), PI, paid to Institution; AstraZeneca, PI, paid to Institution; Pharma Nord, PI, paid to Institution. Travel expenses from NUCANA, Amgen and Mylan. B.G. reports a consulting and advisory role for Pledpharma AB and Isofol AB. M.D. reports a consulting and advisory role for socar research.com and travel expenses from Imotech. M.M.L. reports consulting and advisory role for Solvay, Axcan, Abbvie, Abbott, Mylan, Nordmark, AstraZeneca, Centogene, Roche, ISIS, Ionis and KMG Kliniken. Travel expenses from Falk Foundation, Roche, Abbott and Abbvie, Roche, Menarini, Abbott, Abbvie, Mylan and Nordmark. Research Funding from Deutsche Forschungsgemeinschaft (DFG), Deutsche Krebshilfe/lvlildred Scheel Stiftung, Krupp Foundation, German Federal Ministry of Education and Research (BMBF), European Union (FP7, EFRE, ESF and Horizon 20120), the State Ministy of Education and Research Mecklenburg-Vorpommern, State Minisüry of Economics MV. J.R.M. reports consulting and advisory role for Pfizer, Stock or other ownership from Pacylex Pharmaceuticals Inc. and patent or intellectual property from Pacylex Pharmaceutical Inc. J.M. reports consulting or advisory role for Metonomics Health. Research funding from AstraZeneca, patent or intellectual property from Metanomics Health, Honoraria from Boehringer Ingelheim and Falk Foundation and Travel Expenses from Falk and Celgene. J.S. reports a consulting or advisory role for Amgen. W.G. reports travel expenses from Nucana Biomed. N.C.T. reports travel expenses from Roche and Honoraria from Amgen, Roche and Shire. N.O.E. reports research funding from NUCANA. D.G. reports research funding from Celgene. D.H.P. reports research funding from Nucana Biomed and Honoraria from Bayer, Nucana Biomed, Sictex, Celgene and Baxalta. A.G.S. reports Speakers’ Bureau from Amgen and Honoraria from Amgen, Sanofi, Roche, Lilly, Leo and Celgene. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1
DCTD and RRM1 immunhistochemistry scoring. Representative images of DCTD negative (a), weak (b), moderate (c), and strong (d) expressing tumours, and RRM1 negative (e), weak (f), moderate (g) and strong (h) expressing tumours, respectively
Fig. 2
Fig. 2
Kaplan–Meier survival curves of patient strata dichotomised on DCTD (a, b) and RRM1 (c, d) expression status (negative/weak = 0/1, moderate/strong = 2/3). 5-FU patients treated with 5-fluorouracil and folinic acid, GEM patients treated with gemcitabine, y axis proportion of patients being alive, xaxis weeks from randomisation. p values for log-rank χ2 analyses are given in the respective graph
See this image and copyright information in PMC

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