Journal article
MRE11 as a predictive biomarker of outcome following radiotherapy in bladder cancer
- Abstract:
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Purpose: Organ-confined muscle-invasive bladder cancer is treated with cystectomy or bladder preservation techniques, including radiation therapy. 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 after radiation therapy, 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 2 major clinical trials.
Methods and Materials: Samples from the BCON and BC2001 randomized controlled trials and a cystectomy cohort were stained using automated IHC methods and scored for MRE11 in 3 centers in the United Kingdom.
Results: Despite step-wise creation of scoring cards and standard operating procedures for staining and interpretation, there was poor intercenter scoring agreement (kappa, 0.32; 95% confidence interval, 0.17-0.47). No significant associations between MRE11 scores and cause-specific survival were identified in BCON (n = 132) and BC2001 (n = 221) samples. Reoptimized staining improved agreement between scores from BCON tissue microarrays (n = 116), but MRE11 expression was not prognostic for cause-specific survival.
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 or a reassessment of how DNA-damage response relates to clinical outcomes.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.4MB, Terms of use)
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- Publisher copy:
- 10.1016/j.ijrobp.2019.03.015
Authors
- Publisher:
- Elsevier
- Journal:
- International Journal of Radiation Oncology - Biology - Physics More from this journal
- Volume:
- 104
- Issue:
- 4
- Pages:
- 809-818
- Publication date:
- 2019-03-15
- Acceptance date:
- 2019-03-09
- DOI:
- ISSN:
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0360-3016
- Language:
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English
- Keywords:
- Pubs id:
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pubs:983678
- UUID:
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uuid:bc3f1902-f103-4f02-b827-850c972c9065
- Local pid:
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pubs:983678
- Source identifiers:
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983678
- Deposit date:
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2019-03-21
- ARK identifier:
Terms of use
- Copyright holder:
- Walker et al
- Copyright date:
- 2019
- Notes:
- © The Authors. Published by Elsevier Inc. This is an open access article distributed under the terms of the Creative Commons Attribution Licence
- Licence:
- CC Attribution (CC BY)
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