Prostate Cancer Detection by Molecular Urinalysis
Annual rept., 1 Apr 2005-31 Mar 2006
JOHNS HOPKINS UNIV BALTIMORE MD
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Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related death in the United States. The most common DNA alteration associated with prostate cancer is hypermethylation in the regulatory region of certain genes, particularly in the promoter of the pi-class glutathione-S-transferase GSTP1 gene. Analysis of hypermethylation of other gene promoters in combination has demonstrated high sensitivity and specificity for prostate cancer diagnosis. In this project, we evaluate the feasibility of detection of prostate cancer by molecular urinalysis. Prostatic manipulation from sources such as a biopsy needle, transrectal ultrasound TRUS probe, or digital rectal exam DRE, may cause prostatic DNA to appear in the urine by shedding of neoplastic cells or debris into the prostatic ducts and urethra. The specific impact of prostatic manipulation on the detection of DNA promoter hypermethylation in the urine is unclear, as there are no studies comparing urine obtained before and after prostatic manipulation in identical patients. We hypothesized that voided urine specimens from patients with prostate cancer would be more likely to have detectable DNA promoter hypermethylation immediately after prostate manipulation by TRUS-guided needle biopsy than after DRE. We have compared voided urine samples obtained after extended 15-second DRE with voided urine samples obtained after TRUS-guided needle prostate biopsy from patients with suspected or confirmed prostate cancer using conventional methylation-specific PCR MSP analysis to examine the hypermethylation status of three different gene promoters GSTP1, APC and EDNRB. These loci were chosen because of their high frequency of methylation in prostate cancer specimens. Methylation analysis at multiple genes has also been shown to have diagnostic and prognostic value in prostate cancer.
- Medicine and Medical Research