Clinical Utility of an Epigenetic Assay to Detect Occult Prostate Cancer in Histopathologically Negative Biopsies: Results of the MATLOC Study

Stewart, Grant D.; Neste, Leander Van; Delvenne, Philippe; Delrée, P.; Delga, Agnès; McNeill, S. Alan; O’Donnell, Marie; Clark, James S.; Criekinge, Wim Van; Bigley, Joseph; Harrison, David J.

doi:10.1016/j.juro.2012.08.219

Cited by 193 publications

(161 citation statements)

References 28 publications

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“…GSTP1 methylation alterations can also be detected in histologically negative biopsy samples and can be used to improve the sensitivity of the standard histology work-up for prostate cancer detection (19). These findings suggest that epigenetic alterations in histologically negative biopsy samples may serve as potential markers of prostate cancer diagnosis on a rebiopsy (20). However, while gene-specific hypermethylation, including GSTP1 hypermethylation, has previously been investigated as a possible marker of prostate cancer diagnosis on a rebiopsy (20)(21)(22), to the best of our knowledge, LINE-1 hypomethylation has not.…”

Section: Introductionmentioning

confidence: 94%

Global Hypomethylation (LINE-1) and Gene-Specific Hypermethylation (GSTP1) on Initial Negative Prostate Biopsy as Markers of Prostate Cancer on a Rebiopsy

Zelić

Fiano

Zugna

et al. 2016

Clinical Cancer Research

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Purpose: Men at risk of missed prostate cancer on a negative biopsy often undergo a rebiopsy. We evaluated whether global hypomethylation, measured through LINE-1 methylation, and GSTP1 hypermethylation on a negative biopsy are associated with subsequent prostate cancer diagnosis.Experimental Design: We performed a case-control study nested in an unselected series of 737 men who received at least two prostate biopsies at least three months apart at the Molinette Hospital (Turin, Italy). Two pathology wards were included for replication purposes. The study included 67 cases and 62 controls in Ward 1 and 62 cases and 66 controls in Ward 2. We used pyrosequencing to analyze LINE-1 and GSTP1 methylation in the negative biopsies. Odds ratios (OR) of prostate cancer diagnosis were estimated using conditional logistic regression.Results: After mutual adjustment, GSTP1 hypermethylation was associated with an OR of prostate cancer diagnosis of 5.1 (95% confidence interval: 1.7-14.9) in Ward 1 and 2.0 (0.8-5.3) in Ward 2, whereas an association was suggested only for low LINE-1 methylation levels (<70% vs. 70%-74%) with an OR of 2.1 (0.5-9.1) in Ward 1 and 1.6 (0.4-6.1) in Ward 2. When the two wards were combined the association was stronger for tumors with Gleason score !4þ3 [GSTP1 hypermethylation: 9.2 (2.0-43.1); LINE-1 (<70% vs. 70%-74%): 9.2 (1.4-59.3)]. GSTP-1 alone improved the predictive capability of the model (P ¼ 0.007).Conclusions: GSTP1 hypermethylation on a negative biopsy is associated with the risk of prostate cancer on a rebiopsy, especially of high-grade prostate cancer. Consistent results were found only for extremely low LINE-1 methylation levels.

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Section: Introductionmentioning

confidence: 94%

Global Hypomethylation (LINE-1) and Gene-Specific Hypermethylation (GSTP1) on Initial Negative Prostate Biopsy as Markers of Prostate Cancer on a Rebiopsy

Zelić

Fiano

Zugna

et al. 2016

Clinical Cancer Research

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“…A methylation marker genetic test, ConfirmMDx (MDxHealth), utilizes methylation analysis of glutathione S-transferase pi 1 (GSTP1), adenomatous polyposis coli (APC), and Ras association (RalGDS/AF-6) domain family member 1 (RASSF1) genes from negative biopsies to estimate the likelihood of a repeat biopsy also being negative [78]. The test achieved a 90% negative predictive value (NPV) within 30 mo of the initial biopsy.…”

Section: 3mentioning

confidence: 99%

Genomic Predictors of Outcome in Prostate Cancer

et al. 2015

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“…Clinical validation studies of the methylation assay have included a multi-institutional European study of 498 men undergoing initial negative biopsy followed by repeat biopsy within 30 months. The sensitivity and specificity of the assay for the detection of subsequent PCa were 68 and 64 % with negative predictive value (NPV) of 90 % (95 % CI 87-93 %) [28]. Similarly, in a multi-center US study consisting of 350 men receiving repeat biopsy following initial negative biopsy, the methylation assay was associated with a sensitivity of 62 and 64 % and NPV of 88 % (95 % CI 85-91) [29].…”

Section: Confirmmdxmentioning

confidence: 94%

Clinical Utility of Biomarkers in Localized Prostate Cancer

2016

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A new generation of prostate cancer (PCa) biomarkers has emerged, including diagnostic serum and urine markers aimed at refining the identification high-grade tumors and tissue-based gene expression assays offering prognostic and predictive clinical information. Such tests seek to improve treatment-related decisions at multiple decision points, including initial diagnosis and following initial primary therapy. In this review, we aim to contextualize the body of evidence surrounding these emerging tests, with attention on studies addressing clinical utility.

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Clinical Utility of an Epigenetic Assay to Detect Occult Prostate Cancer in Histopathologically Negative Biopsies: Results of the MATLOC Study

Cited by 193 publications

References 28 publications

Global Hypomethylation (LINE-1) and Gene-Specific Hypermethylation (GSTP1) on Initial Negative Prostate Biopsy as Markers of Prostate Cancer on a Rebiopsy

Global Hypomethylation (LINE-1) and Gene-Specific Hypermethylation (GSTP1) on Initial Negative Prostate Biopsy as Markers of Prostate Cancer on a Rebiopsy

Genomic Predictors of Outcome in Prostate Cancer

Clinical Utility of Biomarkers in Localized Prostate Cancer

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