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.
Written by:
Truong M, Yang B, Livermore A, Wagner J, Weeratunga P, Huang W, Dhir R, Nelson J, Lin DW, Jarrard DF. Are you the author?
University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Reference: J Urol. 2012 Nov 15. pii: S0022-5347(12)05568-1.
doi: 10.1016/j.juro.2012.11.074
PubMed Abstract
PMID: 23159584
UroToday.com Investigative Urology Section
