Evaluation of GSTP1 and APC Methylation As Indicators for Repeat Biopsy in a High-risk Cohort of Men with Negative Initial Prostate Biopsies

Overview

Journal BJU Int

Specialty Urology

Date 2011 Nov 15

PMID 22077694

Citations 40

Authors

Bruce J Trock

Michelle J Brotzman

Leslie A Mangold

Joseph W Bigley

Jonathan I Epstein

David McLeod

Eric A Klein

J Stephen Jones

Songbai Wang

Theresa McAskill

Jyoti Mehrotra

Bhargavi Raghavan

Alan W Partin

Affiliations

Soon will be listed here.

Abstract

Unlabelled: Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Hypermethylation of genes such as glutathione-S-transferase P1 (GSTP1) and adenomatous polyposis coli (APC) occurs with high frequency in prostate tumour tissue but is much less common in the benign prostate; however, the potential value of gene methylation biomarkers as an adjunct to biopsy histopathology has had little study. When measured in histologically benign prostate biopsy tissue, APC gene hypermethylation was found to have high negative predictive value and high sensitivity. GSTP1 hypermethylation was found to have lower performance than APC.

Objective: To evaluate the performance of DNA methylation biomarkers in the setting of repeat biopsy in men with an initially negative prostate biopsy but a high index of suspicion for missed prostate cancer.

Patients And Methods: We prospectively evaluated 86 men with an initial histologically negative prostate biopsy and high-risk features. All men underwent repeat 12-core ultrasonography-guided biopsy. DNA methylation of glutathione-S-transferase P1 (GSTP1) and adenomatous polyposis coli (APC) was determined using tissue from the initially negative biopsy and compared with histology of the repeat biopsy. The primary outcome was the relative negative predictive value (NPV) of APC compared with GSTP1, and its 95% confidence interval (CI).

Results: On repeat biopsy, 21/86 (24%) men had prostate cancer. APC and GSTP1 methylation ratios below the threshold (predicting no cancer) produced a NPV of 0.96 and 0.80, respectively. The relative NPV was 1.2 (95% CI: 1.06-1.36), indicating APC has significantly higher NPV. Methylation ratios above the threshold yielded a sensitivity of 0.95 for APC and 0.43 for GSTP1. Combining both methylation markers produced a performance similar to that of APC alone. APC methylation patterns were consistent with a possible field effect or occurrence early in carcinogenesis.

Conclusions: APC methylation provided a very high NPV with a low percentage of false-negatives, in the first prospective study to evaluate performance of DNA methylation markers in a clinical cohort of men undergoing repeat biopsy. The potential of APC methylation to reduce unnecessary repeat biopsies warrants validation in a larger prospective cohort.

Citing Articles

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Xing W, Li Y, Chen J, Hu Q, Liu P, Ge X Asian Pac J Cancer Prev. 2023; 24(11):3851-3857.

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Epigenetic regulation in lung cancer.

Ramazi S, Dadzadi M, Daddzadi M, Sahafnejad Z, Allahverdi A MedComm (2020). 2023; 4(6):e401.

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Tissue-Based Biomarkers for the Risk Stratification of Men With Clinically Localized Prostate Cancer.

Basourakos S, Tzeng M, Lewicki P, Patel K, Al Hussein Al Awamlh B, Venkat S Front Oncol. 2021; 11:676716.

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Long G, Ouyang W, Zhang Y, Sun G, Gan J, Hu Z Front Mol Biosci. 2021; 8:608369.

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