DNA Hypermethylation Assay Confirms Negative Prostate Cancer Biopsy Results

A commercially available assay that measures the level of hypermethylated DNA in tissue samples was found to accurately identify negative-for-cancer prostate tissues in more than 88% of cases.

Approximately 700,000 men in the USA receive a negative prostate biopsy result; however approximately 25% of these results are false-negative. Under the current standard of care, prostate biopsy procedures collect 10–12 needle biopsy cores on average, effectively sampling less than 1% of a man’s prostate. This approach leaves men at risk of occult cancer, leading to a high rate of repeat biopsies, often on cancer-free men. The MDxHealth (Herstal, Belgium) "ConfirmMDx for Prostate Cancer" assay addresses the unmet medical need for a clinically effective diagnostic test to address this dilemma. "ConfirmMDx for Prostate Cancer" is an epigenetic assay to help distinguish patients who have a true-negative biopsy from those who may have occult cancer. The test helps urologists rule-out prostate cancer-free men from undergoing unnecessary repeat biopsies and, helps rule-in high risk patients who may require repeat biopsies and potential treatment.


In a study to validate the use of the MDxHealth assay, investigators at Johns Hopkins University (Baltimore, MD, USA) evaluated archived negative-for-cancer prostate biopsy core tissue samples from 350 subjects from five urologic centers in the USA. All subjects underwent a repeat biopsy within 24 months with a negative (controls) or positive (cases) histopathological result. The MDxHealth assay profiled methylation levels for the known tumor suppressor genes GSTP1, APC, and RASSF1, which are silenced by hypermethylation and fail to block cancer development.

Results of analysis of the two biopsy specimens from each patient showed that average levels of APC and RASSF1 were about twice as high in the 92 subjects whose second biopsies yielded positive results, as compared to the 228 with two negative biopsies. For GSTP1, the levels were more than eight times higher in the cancerous biopsies.

“Overall, if there is an absence of methylation in all three biomarkers, there is an 88% likelihood you do not have cancer,” said senior author Dr. Jonathan Epstein, professor of pathology, urology, and oncology at Johns Hopkins University. “The test is not 100% of an assurance, but it is a major step forward.”

“Often, one biopsy is not enough to definitively rule out prostate cancer,” said Dr. Epstein. “Our research finds that by looking for the presence or absence of cancer in a different way, we may be able to offer many men peace of mind without putting them through the pain, bleeding and risk of infection that can come with a repeat biopsy. It turns out as many as 20% of men have prostate cancer, even if their first biopsy results are negative. Approximately 40% of men with a negative biopsy go on to receive a second biopsy. Many high-risk men fear sampling errors in their initial biopsy, which often leads to a high rate of follow-up procedures to merely confirm the absence of the disease.”

The study was published in the April 16, 2014, online edition of the Journal of Urology.

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