127 Figure 3. Schematic representation of MS-PCR. In normal and BPH prostate tissues, the gal3 promoter is unmethylated, selleck screening library whereas in stage I and II, it is methylated heavily. However, gal3 promoter is lightly methylated in stage III and IV. Stage-specific cytosine methylation … Early Detection of Prostate Cancer in the Biological Fluids such as Serum and Urine Several studies suggest that prostate cancer can be detected in serum and urine.15,17,120,145 Identification of methylated DNA in urine would be a critical milestone in the development of a non-invasive diagnostic for early stages of prostate cancer. DNA passes into urine and blood through three main routes.146 The first occurs when prostate cells are directly released into the urethra through prostatic ducts.

DNA can also pass into urine by phagocytosis, in which macrophages engulf DNA from necrotic tumor tissue then the macrophages themselves appear in both urine and blood. Lastly, when cell proliferation is accelerated, cellular DNA content can overwhelm phagocytes and directly spill into circulation and urine. The first study of body fluid-based detection involves the analysis of plasma samples of prostate cancer for the detection of GSTP1 promoter hypermethylation. The GSTP1 promoter was found hypermethylated in 72% (23/32) of PCa patients, but none of patients with BPH.140,147 To determine the usefulness of multiple markers in serum samples, Ellinger and colleagues recently performed qMSP to measure hypermethylation of CpG islands in GSTP1, TIG1, PTGS2, and Reprimo.

147 These specific genes have been implicated in the pathogenesis of prostate cancer, and hypermethylation of these genes has been identified in prostate cancer tissue. All four genes displayed higher methylation frequencies in tissues of PCa patients (42.3%, 9.5%, 2.4%, and 1.2%, respectively) compared to BPH patients (7.7%, 0%, 0%, and 0%, respectively) and healthy controls (all 0%).148 Comparing serum DNA of PCa and BPH patients, hypermethylation of either gene was highly specific (92%) but less sensitive (42%�C47%).148 Moreover, hypermethylation of GSTP1 in serum identified 4 patients with incidental prostate cancer recurrence.148 These studies indicate that the detection of GSTP1 promoter methylation may serve as an additional tool to identify PCa in those patients with a high suspicion of disease despite negative biopsies.

Very recently, Sunami et al149 assayed blood from 40 healthy individuals and 83 patients with varying Anacetrapib stages of PCa using MS-PCR of a 3-gene cohort (GSTP1, RASSF1, and RAR��2) and demonstrated detection of 28% cancer patients (24/83). However, a combination of the MS-PCR and PSA assays provided 89% sensitivity. As described above, prostate cancers shed neoplastic cells or debris amenable to DNA analysis. Cairns et al145 first analyzed voided urine samples from patients with prostate cancer and detected GSTP1 hypermethylation in 27% of patients.