Mitochondrial genome deletion aids in the identification of false- and true-negative prostate needle core biopsy specimens.
We report the usefulness of a 3.4-kb mitochondrial genome deletion (3.4 mtdelta) for molecular definition of benign, malignant, and proximal to malignant (PTM) prostate needle biopsy specimens. The 3.4 mtdelta 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 3.4 mtdelta 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 3.4 mtdelta may be useful in defining malignant, benign, and PTM prostate tissues.
Maki
Jennifer
J
Genesis Genomics, Thunder Bay, Canada.
Robinson
Kerry
K
Reguly
Brian
B
Alexander
Jude
J
Wittock
Roy
R
Aguirre
Andrea
A
Diamandis
Eleftherios P
EP
Escott
Nicholas
N
Skehan
Anthony
A
Prowse
Owen
O
Thayer
Robert E
RE
Froberg
M Kent
MK
Wilson
Michael J
MJ
Maragh
Samantha
S
Jakupciak
John P
JP
Wagner
Paul D
PD
Srivastava
Sudhir
S
Dakubo
Gabriel D
GD
Parr
Ryan L
RL
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D001707:Biopsy, Needle / Q000379:methods*; D004272:DNA, Mitochondrial / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005188:False Negative Reactions; D017353:Gene Deletion; D054629:Genome, Mitochondrial; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics; D012372:ROC Curve
D014408:Biomarkers, Tumor; D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm