Prostate Cancer Detected by Methylated Gene Markers in Histopathologically Cancer-Negative Tissues from Men with Subsequent Positive Biopsies
Open Access
- 1 October 2009
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Epidemiology, Biomarkers & Prevention
- Vol. 18 (10), 2717-2722
- https://doi.org/10.1158/1055-9965.epi-09-0068
Abstract
The goal of this retrospective, multicenter study was to evaluate the ability of a newly developed refinement of a quantitative methylation-specific PCR assay to detect prostate cancer in histopathologically negative biopsy samples collected from men who were later positively diagnosed during a follow-up biopsy procedure. Biomarkers tested in the assay included the much-studied glutathione-S-transferase P1 gene and others reported to be frequently methylated in prostate cancer. Core biopsy tissue from subjects with serial negative biopsies served as a negative control to assess assay specificity. As a positive control, biopsy core tissue from patients histopathologically diagnosed with prostate cancer was used to gauge true marker sensitivity in known cancer-containing specimens. Testing was completed in 971 archived paraffin-embedded tissue blocks from 264 men screened for prostate cancer. More samples were initially tested, but due to the advanced age of the paraffinized tissue, DNA quality for quantitative methylation-specific PCR analysis was insufficient in 34% of the available blocks. The glutathione-S-transferase P1 gene has been confirmed as a powerful indicator of the presence of prostate cancer cells. A sensitivity of 52% was observed in the “potentially false-negative first biopsies,” with a corresponding specificity of 85% and the sensitivity in biopsy tissue cores containing histopathologically confirmed prostate cancer was 95%. An even higher sensitivity can be reached with RAR-2β (84%) and APC (72%), with respective specificities of 48% and 50%. Gene methylation was detected in initial, negative biopsy tissue in men who were later diagnosed with prostate cancer. Testing for methylation in histopathologically negative biopsies could improve the early detection of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2717–22)Keywords
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This publication has 30 references indexed in Scilit:
- Predicting Outcomes in Prostate Cancer: How Many More Nomograms Do We Need?Journal of Clinical Oncology, 2007
- Molecular Detection of Localized Prostate Cancer Using Quantitative Methylation-Specific PCR on Urinary Cells Obtained Following Prostate MassageClinical Cancer Research, 2007
- Cancer Statistics, 2007CA: A Cancer Journal for Clinicians, 2007
- Atypical Foci Suspicious but not Diagnostic of Malignancy in Prostate Needle BiopsiesEuropean Urology, 2006
- Diagnostic Value of Systematic Biopsy Methods in the Investigation of Prostate Cancer: A Systematic ReviewJournal of Urology, 2006
- Diagnostic and Prognostic Information in Prostate Cancer with the Help of a Small Set of Hypermethylated Gene LociClinical Cancer Research, 2005
- GSTP1 CpG island hypermethylation as a molecular biomarker for prostate cancerJournal of Cellular Biochemistry, 2003
- Quantitation of DNA Extracted after Micropreparation of Cells from Frozen and Formalin-Fixed Tissue SectionsThe American Journal of Pathology, 2000
- Prostatic Transition Zone Biopsies in Men with Previous Negative Biopsies and Persistently Elevated Serum Prostate Specific Antigen ValuesJournal of Urology, 1995
- Measurement of Prostate-Specific Antigen in Serum as a Screening Test for Prostate CancerNew England Journal of Medicine, 1991