MRE11 as a Predictive Biomarker of Outcome After Radiation Therapy in Bladder Cancer.
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ICR Authors
Authors
Walker, AK
Karaszi, K
Valentine, H
Strauss, VY
Choudhury, A
McGill, S
Wen, K
Brown, MD
Ramani, V
Bhattarai, S
Teo, MTW
Yang, L
Myers, KA
Deshmukh, N
Denley, H
Browning, L
Love, SB
Iyer, G
Clarke, NW
Hall, E
Huddart, R
James, ND
Hoskin, PJ
West, CML
Kiltie, AE
Karaszi, K
Valentine, H
Strauss, VY
Choudhury, A
McGill, S
Wen, K
Brown, MD
Ramani, V
Bhattarai, S
Teo, MTW
Yang, L
Myers, KA
Deshmukh, N
Denley, H
Browning, L
Love, SB
Iyer, G
Clarke, NW
Hall, E
Huddart, R
James, ND
Hoskin, PJ
West, CML
Kiltie, AE
Document Type
Journal Article
Date
2019-07-15
Date Accepted
2019-03-09
Abstract
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.
Citation
International journal of radiation oncology, biology, physics, 2019, 104 (4), pp. 809 - 818
Source Title
Publisher
ELSEVIER SCIENCE INC
ISSN
0360-3016
eISSN
1879-355X
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Research Team
ICR-CTSU Urology and Head and Neck Trials Team
Clinical Academic Radiotherapy (Huddart)
Prostate and Bladder Cancer Research
Clinical Academic Radiotherapy (Huddart)
Prostate and Bladder Cancer Research