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Accurate prediction of repeat prostate biopsy outcomes by a mitochondrial DNA deletion assay

A Corrigendum to this article was published on 12 November 2013

Abstract

Several cancers are characterized by large-scale mtDNA deletions. We previously provided evidence that one of these deletions has potential utility in resolving false from true-negative prostate needle biopsies. This study was to assess the clinical value of this deletion in predicting re-biopsy outcomes. We used a quantitative polymerase chain reaction assay to measure the levels of the deletion in individual negative needle biopsies from 101 patients who had a repeat biopsy within a year with known outcomes. Using an empirically established cycle threshold (Ct) cutoff of 31, and the lowest Ct for each patient as diagnostic of prostate cancer, as well as the histopathologic diagnosis on second biopsy, we calculated the clinical performance of the deletion. The Ct cutoff at 31 gave a sensitivity and specificity of 84 and 54%, respectively, with the area under a receiver-operating characteristics curve of 0.749. The negative predictive value was 91%. The assay was able to predict the presence of a missed tumor in 17 out of 20 men a year before diagnosis. This ancillary test appears to identify men who do not require a repeat biopsy with a high degree of certainty. The results suggest that the majority of men with atypical small acinar proliferation have a concurrent missed tumor and therefore require close monitoring for early detection.

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Acknowledgements

This work was supported in part by grants from Industry Canada (FedNor), Sudbury, Canada, and Northern Ontario Heritage Fund Corporations (NHOFC), Sault Ste Marie. We thank the patients and their physician for the samples.

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Correspondence to G D Dakubo.

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The authors Kerry Robinson, Jennifer Creed, Brian Reguly, Cortney Powell, Roy Wittock, Daniel Klein, Andrea Maggrah, Ryan L. Parr and Gabriel D. Dakubo work for and own stocks in Genesis Genomics. Laurence Klotz is a paid consultant with Genesis Genomics.

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Robinson, K., Creed, J., Reguly, B. et al. Accurate prediction of repeat prostate biopsy outcomes by a mitochondrial DNA deletion assay. Prostate Cancer Prostatic Dis 13, 126–131 (2010). https://doi.org/10.1038/pcan.2009.64

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