OUP user menu

Mitochondrial Genome Deletion Aids in the Identification of False- and True-Negative Prostate Needle Core Biopsy Specimens

Jennifer Maki, Kerry Robinson MSc, Brian Reguly, Jude Alexander MSc, Roy Wittock MSc, Andrea Aguirre MSc, Eleftherios P. Diamandis MD, PhD, Nicholas Escott MD, Anthony Skehan MD, PhD, Owen Prowse MD, Robert E. Thayer PhD, M. Kent Froberg MD, Michael J. Wilson PhD, Samantha Maragh, John P. Jakupciak PhD, Paul D. Wagner PhD, Sudhir Srivastava PhD, Gabriel D. Dakubo MB, ChB, Ryan L. Parr PhD
DOI: http://dx.doi.org/10.1309/UJJTH4HFEPWAQ78Q 57-66 First published online: 1 January 2008


We report the usefulness of a 3.4-kb mitochondrial genome deletion (3.4mt ) for molecular definition of benign, malignant, and proximal to malignant (PTM) prostate needle biopsy specimens. The 3.4mt was identified through long-extension polymerase chain reaction (PCR) analysis of frozen prostate cancer samples. A quantitative PCR assay was developed to measure the levels of the 3.4mt in clinical samples. For normalization, amplifications of a nuclear target and total mitochondrial DNA were included. Cycle threshold data from these targets were used to calculate a score for each biopsy sample. In a pilot study of 38 benign, 29 malignant, and 41 PTM biopsy specimens, the difference between benign and malignant core biopsy specimens was well differentiated (P < .0001), with PTM indistinguishable from malignant samples (P = .833). Results of a larger study were identical. In comparison with histopathologic examination for benign and malignant samples, the sensitivity and specificity were 80% and 71%, respectively, and the area under a receiver operating characteristic (ROC) curve was 0.83 for the deletion. In a blinded external validation study, the sensitivity and specificity were 83% and 79%, and the area under the ROC curve was 0.87. The 3.4mt may be useful in defining malignant, benign, and PTM prostate tissues.

Key Words:
  • mtDNA deletion
  • Prostate biopsy
  • False-negative biopsy result
  • Sensitivity
  • Specificity
  • Field cancerization