Employing the Epigenetic Field Defect to Detect Prostate Cancer in Biopsy-Negative Patients.

Publication Type:

Journal Article

Source:

The Journal of urology (2012)

Keywords:

December 2012, Public Health Sciences Division

Abstract:

PURPOSE: To determine whether a novelcombination of fielddefect DNA methylation markers can predict the presence of PCa using histologically normal transrectal ultrasound-guided biopsy cores. MATERIALS AND METHODS: Methylation was assessed using quantitative pyrosequencing in a training set consisting of 65 non-tumor associated (NTA) and tumor associated (TA) prostate tissues from the University of Wisconsin. Amultiplex model was generated using multivariate logistic regression and externally validated in a blinded fashion using a set of 47 NTA and TA biopsy specimens from the University of Washington. RESULTS: Robust methylation differences were observed for all genes at all CpGs assayed (p<0.0001). Regression models incorporating individual genes (EVX1, CAV1, and FGF1) and a gene combination (EVX1 and FGF1) discriminated between NTA and TA tissues in the original training set (AUC 0.796-0.898, p<0.001). Upon external validation, uniplex models incorporating EVX1, CAV1, or FGF1 discriminated between TA and NTA biopsy-negative specimens with an AUC of 0.702, 0.696, and 0.658, respectively (p<0.05). Furthermore, amultiplex model (EVX1 and FGF1) identified PCa patients with an AUC of 0.774 (p=0.001) and had a negative predictive value of 0.909.Comparison between 2 separate cores within patients in this validation set revealed similar methylation defects indicating a widespread field defect was being detected. CONCLUSIONS: A widespread epigenetic fielddefect can be utilized to detect the existence of PCa in patients with histologically negative biopsies. This assay is unique in that it detects alterations in non-tumor cells. With further validation, this markercombination (EVX1 and FGF1) has the potential to decrease the need for repeated prostate biopsies, a procedure associated with cost and complications.