Walker, AK;
Karaszi, K;
Valentine, H;
Strauss, VY;
Choudhury, A;
McGill, S;
Wen, K;
... Kiltie, AE; + view all
(2019)
MRE11 as a predictive biomarker of outcome following radiotherapy in bladder cancer.
International Journal of Radiation Oncology - Biology - Physics
, 104
(4)
pp. 809-818.
10.1016/j.ijrobp.2019.03.015.
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Abstract
Purpose Organ-confined muscle-invasive bladder cancer (MIBC) is treated with cystectomy or bladder preservation techniques, including radiotherapy. There are currently no biomarkers to inform management decisions and aid patient choice. Previously we showed high levels of MRE11 protein, assessed by immunohistochemistry (IHC), predicted outcome following radiotherapy but not cystectomy. Therefore, we sought to develop the MRE11 IHC assay for clinical use and define its relationship to clinical outcome in samples from two major clinical trials. Methods and Materials Samples from the BCON and BC2001 randomised controlled trials and a cystectomy cohort were stained using automated IHC methods and scored for MRE11 in three UK centres. Results Despite step-wise creation of scoring cards and standard operating procedures for staining and interpretation, there was poor inter-centre scoring agreement (Kappa 0.32, 95% CI 0.17-0.47). There were no significant associations between MRE11 scores and cause-specific survival (CSS) identified in BCON (n=132) and BC2001 (n=221) samples. Re-optimised staining improved agreement between scores from BCON tissue microarrays (n=116), but MRE11 expression was not prognostic for CSS. Conclusions Manual IHC scoring of MRE11 was not validated as a reproducible biomarker of radiation-based bladder preservation success. There is a need for automated quantitative methods and/or a reassessment of how DNA-damage response relates to clinical outcomes.
| Type: | Article |
|---|---|
| Title: | MRE11 as a predictive biomarker of outcome following radiotherapy in bladder cancer |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ijrobp.2019.03.015 |
| Publisher version: | https://doi.org/10.1016/j.ijrobp.2019.03.015 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, and provide a link to the Creative Commons license. You do not have permission under this license to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. |
| Keywords: | predictive biomarkers, bladder cancer, immunohistochemistry, MRE11NBN |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10072456 |
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