Prostate cancer (PCA) is the most commonly diagnosed cancer in American males and the second leading cause of cancer deaths. Current screening modalities are less than perfect, lacking the sensitivity and specificity for the optimal detection of organized confined potentially curable disease. Recent reports have identified two candidate markers for the early detection of prostate cancer: telomerase and methylation status. It is well established that the hallmarks of oncogenic transformation include general chromosome instability, widespread aberrations in cytosine methylation patterning and up-regulation of the telomerase system. A link between telomerase expression and chromosome stability has been recognized for some time, and links between chromosome instability and cytosine methylation have recently been firmly established. Our recent tumor biology studies suggest a link between telomerase over-expression and aberrations in methylation patterning. Thus, providing the basis for the use of these two markers in the detection of tumor and tumor progression. Our long term goal is to validate a set of markers of telomerase over- expression and local methylation change that can be used in providing a highly reliable test for detection and prognosis of prostate cancer using cells present in expressed prostatic fluid obtained from patients with elevated PSA and/or abnormal digital rectal exam (DRE). Our hypothesis is that methylation status at the androgen receptor gene, pi-class glutathione-S transferase gene GSTP1, L1 repetitive, or subtelomeric DNA sequences, or subtelomeric DNA sequences coupled with telomerase component levels in expressed prostatic secretion (EPS) will be reliable predictors of the presence or absence of prostate cancer. In addition, we believe that the methylation status of these various genes and sequences will provide prognostic information comparable to the Gleason's score on the prostate biopsy. EPS will be collected on all patients undergoing a TRUSP and biopsy for the evaluation of PCA. The EPS will be tested for the presence of the telomerase components and for the methylation patterns of the AR, GSTP1 gene, L1 repetitive elements and subtelomeric DNA sequences. We will combined the methylation results with the results of the EPS telomerase in patients with prostatic cancer and then compare this EPS profile to the stage and grade of the disease.
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