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Methylation may help avoid a repeat biopsy for prostate cancer
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SAN FRANCISCO – Methylation of GSTP1 and APC genes could be a biomarker for prostate cancer with the potential to help some men avoid the need for second biopsy in high-risk patients who had a negative first biopsy.
Many men receive unnecessary second biopsies, according to Bruce Trock, PhD, associate professor in the Brady Urological Institute at Johns Hopkins Medical Institutions in Baltimore. However, identifying the men who can avoid a repeat biopsy is currently not possible. Only about 30% of men who have a negative first biopsy are diagnosed with prostate cancer on second biopsy, he said at the 2008 Genitourinary Cancers Symposium.
Trock and colleagues performed DNA methylation on prospectively collected tissue samples from 86 men with negative initial biopsies, but a high index of suspicion for prostate cancer. All men had repeat biopsy within two years. On the repeat biopsy, 21 men had prostate cancer.
The negative predictive value of the initial biopsy was 76%. GSTP1 and APC methylation had a negative predictive value of 96%. When excluding men who had atypia on first biopsy (urologists would generally repeat biopsies on these men), the negative predictive value was 100%.
"If these preliminary results are validated, they suggest that about 30% of men with high-risk features after an initial negative biopsy could avoid repeat biopsy," Trock said during his presentation. "For validation studies, it may also be useful to evaluate incorporating APC methylation into nomograms to predict negative biopsies." – by Emily Shafer
For more information:
- Trock B, Epstein D, McLeod D, et al. #2. Presented at: 2008 Genitourinary Cancers Symposium; Feb. 14-16, 2008; San Francisco.
We have a clinical dilemma when we have a patient with an elevated PSA, but a negative biopsy. That dilemma is created by the fact that we know a biopsy does not sample the entire prostate. There is a substantial (20% to 30%) chance that on second biopsy, cancer missed by the first biopsy will be detected. The question is, can we develop a tissue or other biological-based marker that would allow us to test the tissue on the first biopsy and identify the likelihood of no cancer being present? If we could build that with confidence, we'd know whether another biopsy would be necessary.
This study is based on the observation that prostate cancer has certain genes that are turned off by methylation in the promoter region. In prostate cancer, the GSTP1 gene is turned off by methylation in almost 100% of patients. The purpose of this study was to determine whether methylation in that gene and the APC gene increased the likelihood of finding cancer on a second biopsy, and whether no methylation decreased the likelihood of finding cancer. In this subset of patients, these markers increased the utility of the first biopsy from about 70% to about 96%. Follow-up studies in a larger number of patients are currently underway to validate this test. The ultimate clinical significance is that if you can do this on the initial biopsy, you can decide whether a second biopsy is necessary in high-risk men, such as those with a high PSA level.
– Eric Klein, MD
Section Head of Urologic Oncology, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation