title: Accurate prediction of repeat prostate biopsy outcomes by a mitochondrial DNA deletion assay.
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.
authors.affiliation: Genesis Genomics, Thunder Bay, ON, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Robinson
authors.forename: J
authors.initials: J
authors.lastname: Creed
authors.forename: B
authors.initials: B
authors.lastname: Reguly
authors.forename: C
authors.initials: C
authors.lastname: Powell
authors.forename: R
authors.initials: R
authors.lastname: Wittock
authors.forename: D
authors.initials: D
authors.lastname: Klein
authors.forename: A
authors.initials: A
authors.lastname: Maggrah
authors.forename: L
authors.initials: L
authors.lastname: Klotz
authors.forename: R L
authors.initials: RL
authors.lastname: Parr
authors.forename: G D
authors.initials: GD
authors.lastname: Dakubo
mesh_terms: D001707:Biopsy, Needle; D004272:DNA, Mitochondrial / Q000235:genetics*; D005188:False Negative Reactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial