[-2]Proenzyme Prostate Specific Antigen for Prostate Cancer Detection: A National Cancer Institute Early Detection Research Network Validation Study

Departments of Pathology and Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
The Journal of urology (Impact Factor: 3.75). 09/2008; 180(2):539-43; discussion 543. DOI: 10.1016/j.juro.2008.04.015
Source: PubMed

ABSTRACT This study evaluated the [-2]proenzyme prostate specific antigen serum marker using a blinded reference specimen set from 3 National Cancer Institute Early Detection Research Network centers from men with an indication for prostate biopsy.
Serum was collected before biopsy from 123 men with no prior biopsy or prostate cancer history. Specimens (cancer cases 51%, noncancer controls 49%) were selected equally from the 3 sites, and analyzed for prostate specific antigen, free prostate specific antigen, [-2]proenzyme prostate specific antigen, benign prostate specific antigen and testosterone (Beckman Coulter ACCESS(R) analyzer).
There was no difference in total prostate specific antigen concentrations (noncancer 6.80 +/- 5.20 ng/ml, cancer 6.94 +/- 5.12 ng/ml) among the groups. Overall %[-2]proenzyme prostate specific antigen had the greatest area under the curve (AUC 0.69) followed by percent free prostate specific antigen (AUC 0.61). For %[-2]proenzyme prostate specific antigen maximal sensitivity was 60% and specificity was 70%. A logistic regression model combining prostate specific antigen, benign prostate specific antigen, percent free prostate specific antigen, %[-2]proenzyme prostate specific antigen, [-2]proenzyme prostate specific antigen/benign prostate specific antigen and testosterone had an AUC of 0.73. In the 2 to 10 ng/ml prostate specific antigen range %[-2]proenzyme prostate specific antigen and the model had the largest AUC (0.73). The AUC for percent free prostate specific antigen was 0.53. Specificities for %[-2]proenzyme prostate specific antigen, the logistic regression model and percent free prostate specific antigen at 90% sensitivity were 41%, 32% and 18%, and at 95% sensitivity were 31%, 26% and 16%, respectively.
%[-2]proenzyme prostate specific antigen was the best predictor of prostate cancer detection compared to percent free prostate specific antigen, particularly in the 2 to 10 ng/ml total prostate specific antigen range. These findings provide a rationale for broader validation studies to determine whether %[-2]proenzyme prostate specific antigen alone can replace other molecular prostate specific antigen assays (such as percent free prostate specific antigen) for improving the accuracy of prostate cancer early detection. These findings also support the usefulness of well characterized, carefully collected reference sets to evaluate new biomarkers.

  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper reports the development of underwater flexible shear-stress sensor skins that enable not only the acquisition of shear-stress distributions on non-planar surfaces but also a reliable packaging scheme. The sensor skin fabrication consists of two steps: the fabrication of shear-stress sensors on silicon wafers and the fabrication of flexible skins by forming arrays of silicon islands sandwiched by two polyimide layers. The fabricated sensor skin has been packaged on a metal plug and bonding pads were folded to the back side through a slit on the plug. Wire bonding was performed on the back side to improve the reliability and minimize flow interference. The packaged sensor skin has been installed on a water tunnel and successfully tested.
    Micro Electro Mechanical Systems, 2004. 17th IEEE International Conference on. (MEMS); 02/2004
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Currently, serum prostate-specific antigen (PSA) is used for the early detection of prostate cancer despite its low specificity in the range of 4-10 ng/mL. Because aberrant glycosylation is a fundamental characteristic of tumor genesis, the objective of this study was to investigate whether changes in PSA glycosylation may be used to improve the cancer specificity of PSA. We developed five lectin immunosorbant assays to analyze the glycosylation patterns of PSA in serum. Each assay sandwiches serum PSA between a PSA monoclonal antibody and a biotinylated lectin and then tags the biotin complex using a streptavidin SULFO TAG for electrochemiluminescence detection. Low limits of detection (0.04-1.35 ng/mL), good reproducibility (%CVs < 10%), and direct analysis of PSA glycosylation in sera suggest these assays may have a potential role in improving PSA's cancer specificity. Clinical performance was evaluated in 52 human subjects (26 cancer and 26 noncancer). ROC analysis showed that the total SNA assay (AUC = 0.71) appeared to perform better than percent free PSA (AUC = 0.54) in its diagnostic gray zone between 10 and 20% in a subset of 21 subjects. A separate study of 16 additional subjects showed similar findings.
    Journal of Proteome Research 12/2008; 8(2):613-9. DOI:10.1021/pr8007539 · 5.00 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The prostate gland secretes many proteins in a prostatic fluid that combines with seminal vesicle derived fluids to promote sperm activation and function. Proximal fluids of the prostate that can be collected clinically are seminal plasma and expressed-prostatic secretion (EPS) fluids. EPS represents the fluid being secreted by the prostate following a digital rectal prostate massage, which in turn can be collected in voided urine post-exam. This collection is not disruptive to a standard urological exam, and it can be repeatedly collected from men across all prostatic disease states. A direct EPS fluid can also be collected under anesthesia prior to prostatectomy. While multiple genetic assays for prostate cancer detection are being developed for the shed epithelial cell fraction of EPS urines, the remaining fluid that contains many prostate-derived proteins has been minimally characterized. Approaches to optimization and standardization of EPS collection consistent with current urological exam and surgical practices are described, and initial proteomic and glycomic evaluations of the of EPS fluid are summarized for prostate specific antigen and prostatic acid phosphatase. Continued characterization of the prostate specific protein components of EPS urine combined with optimization of clinical collection procedures should facilitate discovery of new biomarkers for prostate cancer.
    Journal of proteomics 02/2009; 72(6):907-17. DOI:10.1016/j.jprot.2009.01.007 · 3.93 Impact Factor
Show more


Available from