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Mitochondrial Genome Deletion Aids in the Identification of Both False and True Negative Prostate Needle Core Biopsies

Published

Author(s)

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

Abstract

We report the utility of a 3.4kb mtgenome deletion (3.4mt?) for molecular definition of benign, malignant and proximal to malignant (PTM) needle biopsies. The 3.4mt_ was identified through long extension PCR analysis of frozen PCa samples. A quantitative PCR assay was developed to measure the levels of the 3.4mt_ in clinical samples. For the purpose of normalization, amplifications of tumor necrosis factor and total mtDNA 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 biopsies, the difference between benign and malignant core biopsies were well differentiated (p<0.0001), with PTM indistinguishable from malignant samples (p=0.833). Results of a larger study were identical to the pilot study. In comparison to histopathology, the sensitivity and specificity were 80% and 71% respectively, and the area under an ROC curve was 0.83. In a blinded validation study at NIST, the sensitivity and specificity were 83% and 79%, and the area under the ROC curve was 0.84. The statistical discrimination between the groups suggests that the 3.4mt_ may be of use in defining malignant, PTM and benign prostate tissue.
Citation
American Journal of Clinical Pathology
Volume
129
Issue
1

Keywords

false negative biopsy, field cancerization, mtDNA deletion, prostate biopsy, sensitivity, specificity

Citation

Maki, J. , Robinson, K. , Reguly, B. , Alexander, J. , Wittock, R. , Aguirre, A. , Diamandis, E. , Escott, N. , Skehan, A. , Prowse, O. , Thayer, R. , Froberg, K. , Wilson, M. , Maragh, S. , Jakupciak, J. , Wagner, P. , Srivastava, S. , Dakubo, G. and Parr, R. (2008), Mitochondrial Genome Deletion Aids in the Identification of Both False and True Negative Prostate Needle Core Biopsies, American Journal of Clinical Pathology (Accessed May 19, 2024)

Issues

If you have any questions about this publication or are having problems accessing it, please contact reflib@nist.gov.

Created January 5, 2008, Updated October 12, 2021