Markers for Early Detection of Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Study type: Observational

Summary: 
      This study will determine whether certain gene alterations can serve as markers for early
      detection of prostate cancer. Prostate cancer is often diagnosed by detecting high levels of
      a protein called prostate-specific antigen (PSA) in the blood. Other conditions can also
      cause elevated PSA levels, however, so that additional tests are needed to distinguish
      between benign and cancerous prostate conditions.

      Patients between 40 and 75 years of age who are referred to Howard University Hospital in
      Washington, D.C., or Madigan Army Medical Center in Tacoma, Washington, for ultrasound and
      needle biopsy to diagnose prostate cancer may be eligible for this study.

      Participants will undergo the following procedures at the time of the biopsy visit:

        -  Blood collection: Patients have 10 milliliters (2 teaspoons) of blood drawn.

        -  Prostate massage: Patients have a rectal examination and prostate massage. For the
           latter procedure, the physician lightly massages the prostate gland for about 15
           seconds. After the massage, the patient provides a urine specimen.

        -  Biopsy: A small sample of tumor tissue is removed surgically for examination under the
           microscope.

      Patients whose initial biopsy does not show cancer cells, but who are advised to have a
      repeat biopsy in the future will give a blood, urine, and biopsy specimen at the time of the
      next biopsy.

      Patients who are diagnosed with prostate cancer and undergo surgery to remove the tumor will
      have a small sample of tumor tissue set aside for this study to look for substances that may
      help predict prostate cancer.
    

Detailed description: 
      In the U.S., screening by prostate-specific antigen (PSA) is widespread and considered to be
      an effective early detection screen for prostate cancer although there are some problems
      associated with its use. Only about 30-40% of men with elevated PSA are diagnosed with cancer
      on initial biopsy. The other 60-70% are diagnosed with either benign prostatic hyperplasia or
      low-or high-grade prostatic intraepithelial neoplasia (LGPIN or HGPIN). Due to their
      persistent elevated PSA levels, men undergo repeat biopsies where many are subsequently
      diagnosed with cancer (the false negative rate for biopsies with pathological diagnoses of
      benign or LGPIN has been reported to be 13-19% and for HGPIN from 50-70%). We propose to
      conduct a pilot study to evaluate whether (i) the addition of molecular markers (e.g.,
      tumor-specific gene methylation of GSTPI, CD44, Annexin II, and Caveolin 1) detectable in
      serum and/or urine sediments after prostatic massage can improve the prediction of prostate
      cancer and (ii) addition of tumor-specific gene methylation detectable in core-needle biopsy
      specimens can improve the sensitivity of core-needle biopsy in the diagnosis of prostate
      cancer among patients screened at two Urology clinics located at Howard University,
      Washington, DC and Madigan Army Medical Center, Tacoma, WA. Preliminary studies have shown
      detection of hypermethylated genes in urine sediments after prostatic massage in men with
      elevated PSA (greater than 4ng/ml) improved the specificity of PSA from 73% to 98%. Further,
      DNA hypermethylation of tumor-specific genes was also identified in serum. In our laboratory,
      we have developed assays for evaluating DNA hypermethylation of several genes shown to be
      important in prostate carcinogenesis. These assays are highly sensitive (able to detect down
      to about 20 tumor cells with methylated DNA) and specific (can distinguish methylated from
      normal DNA from in a ratio of 1 tumor cell in 10,000 normal cells), and could serve to add
      value to current prostate cancer screening modalities.
    

Keywords: Methylation; Genes; Screening; Prospective; Diagnosis