AUA 2013 - Session Highlights: Employing the epigenetic field effect to detect prostate cancer in biopsy-negative patients

SAN DIEGO, CA USA (UroToday.com) - Patients at high suspicion for prostate cancer, but a negative prostate needle biopsy, pose a difficult diagnostic dilemma and often require additional radiographic, laboratory, and imaging-guided interventions to arrive at an acceptable diagnosis and treatment plan.

Dr. Matthew Truong and colleagues presented a study which capitalized on the concept of “field effect,” used to explain multifocality and presence of preneoplastic molecular alterations in histologically normal tissues associated with tumor. Authors focused on a combination of DNA methylation markers and their ability to predict the presence of prostate cancer in patients with histologically normal needle biopsy cores.

Using quantitative pyrosequencying to assess methylation, 65 non-tumor associated (NTA) and tumor associated (TA) prostate tissue specimens were used. A multivariable model was developed and validated in 47 NTA and TA biopsy specimens from an external institution. Presence of prostate cancer in TA and NTA tissues was ruled out by an experienced uropathologist.

The authors observed robust methylation differences for all individual genes, and regression models with EVX1, CAV1, FGF1, and a combination of EVX1 and FGF1, were able to discriminate between TA and NTA tissue in the training set. Uniplex models yielded statistically significant discrimination at external validation (AUC 0.658 – 0.796, p < 0.05). A multiplex model (EVX1 and FGF1) identified prostate cancer patients with an AUC=0.774 (p=0.001) and a negative predictive value of 0.909.

They demonstrated the potential to utilize epigenetic field effect in stratifying patients with a negative needle biopsy. Pending further validation, need for further imaging and biopsy evaluation of these patients may be minimized, thus avoiding additional morbidity, anxiety, and cost.

Presented by Matthew Truong, Bing Yang, Andrew Livermore, Jennifer Wagner, Pushpa Weeratunga, Wei Huang, Rajiv Dhir, Joel Nelson, Daniel Lin, and David Jarrard at the American Urological Association (AUA) Annual Meeting - May 4 - 8, 2013 - San Diego Convention Center - San Diego, California USA


Reported for UroToday.com by Serge Ginzburg, MD 

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