Mitochondrial genome deletion aids in the identification of false- and true-negative prostate needle core biopsy specimens

Jennifer Maki, Kerry Robinson, Brian Reguly, Jude Alexander, Roy Wittock, Andrea Aguirre, Eleftherios P. Diamandis, Nicholas Escott, Anthony Skehan, Owen Prowse, Robert E. Thayer, M. Kent Froberg, Michael J Wilson, Samantha Maragh, John P. Jakupciak, Paul D. Wagner, Sudhir Srivastava, Gabriel D. Dakubo, Ryan L. Parr

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

We report the usefulness of a 3.4-kb mitochondrial genome deletion (3.4mtδ) for molecular definition of benign, malignant, and proximal to malignant (PTM) prostate needle biopsy specimens. The 3.4mtδwas 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 3.4mtδin 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 3.4mtδmay be useful in defining malignant, benign, and PTM prostate tissues.

Original languageEnglish (US)
Pages (from-to)57-66
Number of pages10
JournalAmerican journal of clinical pathology
Volume129
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • False-negative biopsy result
  • Field cancerization
  • MtDNA deletion
  • Prostate biopsy
  • Sensitivity
  • Specificity

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