Molecular assays for the detection of prostate tumor derived nucleic acids in peripheral blood.

Background: Prostate cancer is the second leading cause of cancer mortality in American men. Although serum PSA testing is widely used for early detection, more specific prognostic tests are needed to guide treatment decisions. Recently, the enumeration of circulating prostate epithelial cells has been shown to correlate with disease recurrence and metastasis following definitive treatment.

Detailed analysis of histopathological parameters in radical prostatectomy specimens and PCA3 urine test results.

Background: Due to the drawbacks of serum prostate-specific antigen, there is an ongoing search for new diagnostic and prognostic prostate cancer (PCa) markers. PCA3 has proven to be of value in the diagnosis of PCa. However, so far few attempts have been made to investigate the prognostic value of PCA3.

Twenty Years of PSA: From Prostate Antigen to Tumor Marker.

The measurement of prostate-specific antigen in serum is credited with dramatic advances in the early detection of men with prostatic carcinoma. This report summarizes the history of biochemical research and the current understanding and application of prostate-specific antigen in prostate cancer diagnostics.

Molecular PCA3 diagnostics on prostatic fluid.

Background: The PCA3 test on urine can improve specificity in prostate cancer (PCa) diagnosis and could prevent unnecessary prostate biopsies. In this study, we evaluated the PCA3 test on prostatic fluid and compared this with the PCA3 test on urine in a clinical research setting.

Methods: Prostatic fluid and urine samples from 67 men were collected following digital rectal examination (DRE).

Immunohistochemical staining of precursor forms of prostate-specific antigen (proPSA) in metastatic prostate cancer.

Precursors of prostate-specific antigen (proPSA) have been previously shown to be more concentrated in prostate cancer tissue. This study characterizes the immunohistochemical staining (IHS) of proPSA forms in metastatic prostate cancer compared with prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). A tissue microarray, consisting of 74 cases of metastatic prostate carcinoma and control tissues, was used.

Evaluation of precursor prostate-specific antigen isoform ratios in the detection of prostate cancer.

Objective: Disease-associated isoforms of the prostate-specific antigen (PSA) have recently been identified. We evaluated the efficacy of using precursor isoforms of PSA (pPSA) and their ratios for the detection of prostate cancer.

Methods: Serum concentrations of [-2], [-4], and [-7]pPSA, BPSA, and free PSA (fPSA) were retrospectively measured in 43 selected men.

Additional use of [-2] precursor prostate-specific antigen and "benign" PSA at diagnosis in screen-detected prostate cancer.

Objectives: To evaluate the adjuvant clinical use of [-2] precursor prostate-specific antigen ([-2]pPSA), which is associated with prostate cancer (PCa), and "benign" PSA, related to benign prostatic hyperplasia, in selecting a treatment strategy in patients with screen-detected PCa.

Methods: Research-use immunoassays (Beckman Coulter) were used to measure [-2]pPSA, sum [-7, -5, -4, and -2]pPSA, and benign PSA from the frozen serum of participants from the screen arm of the European Randomized Study of Screening for Prostate Cancer, section Rotterdam, diagnosed with PCa with a serum PSA level lower than 15 ng/mL. We compared men with relatively benign PCa (Epstein's criteria; group 1) and men with arbitrarily defined aggressive PCa characteristics (Gleason score greater than 4 + 4 and more than four cores with PCa invasion or pT3C disease; group 2).

Comparison of predictive accuracy for pathologically organ confined clinical stage T1c prostate cancer using human glandular kallikrein 2 and prostate specific antigen combined with clinical stage and Gleason grade.

Purpose: Previously human glandular kallikrein 2 (hK2) has been implicated to predict pathologically organ confined prostate cancer (PCa) in patients with stage T2 disease. Now we evaluated the usefulness of hK2, as measured by 2 entirely different immunoassay designs, to enhance the discrimination of pathologically organ from nonorgan confined clinical stage T1c PCa.

Materials And Methods: A consecutive series of pretreatment serum from 148 men with clinical stage T1c PCa was used in 2 equally sensitive and specific methods to measure total hK2 with independent reagents and entirely different assay designs.

Clinical utility of proPSA and "benign" PSA when percent free PSA is less than 15%.

Objectives: To investigate the clinical utility of the subforms of free prostate-specific antigen (PSA), namely proPSA and "benign" PSA (BPSA), to improve cancer detection when the percent free PSA level is less than 15%. Percent free PSA, while maintaining sensitivity, has greatly improved the specificity of PSA for the early detection of prostate cancer. A low percent free PSA value indicates a greater risk of cancer, but only 30% to 50% of men with percent free PSA levels of less than 15% actually have cancer at biopsy.

Are multiple markers the future of prostate cancer diagnostics?

Prostate specific antigen (PSA) is the most successful and widely employed cancer serum marker in use today. There is growing evidence that the introduction of wide PSA screening and earlier detection can result in decreased cancer mortality associated with a decline in metastatic disease. PSA circulates in a number of distinct forms.

Tumor-associated forms of prostate specific antigen improve the discrimination of prostate cancer from benign disease.

Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer, but has limited specificity for distinguishing early prostate cancer(PCa) from benign disease since serum PSA can leak from both tumor and prostate tissues with benign disease. Molecular forms of free PSA have been identified that are associated with either benign or malignant prostate tissues. BPSA is a form of free PSA that is associated with benign prostatic hyperplasia(BPH), the predominant benign disease in men.

Serum BPSA outperforms both total PSA and free PSA as a predictor of prostatic enlargement in men without prostate cancer.

Objectives: To determine whether the serum concentration of BPSA, a distinct form of free prostate-specific antigen (PSA) enriched in the nodular transition zone (TZ) tissue of benign prostatic hyperplasia (BPH), can predict TZ volume and diagnose BPH-associated prostatic enlargement in patients without prostate cancer.

Methods: We studied 91 consecutive patients without prostate cancer who underwent a 10-core or greater biopsy of the prostate. The associations between prostate volume, age, International Prostate Symptom Score, and serum concentrations of PSA, free PSA, and BPSA were evaluated by receiver operating characteristic curve and linear and binary logistic regression analyses.

Prostate cancer detection in the prostate specific antigen range of 2.0 to 3.9 ng/ml: value of percent free prostate specific antigen on tumor detection and tumor aggressiveness.

Purpose: We evaluated the positive predictive value and cancer detection rate in the prostate specific antigen (PSA) range of 2.0 to 3.9 ng/ml and assessed the value of percent free (F) PSA (FPSA) on tumor detection and tumor aggressiveness in this low PSA range.

Serum pro-prostate specific antigen preferentially detects aggressive prostate cancers in men with 2 to 4 ng/ml prostate specific antigen.

Purpose: Pro forms of prostate specific antigen (PSA) have been reported to be more cancer specific markers of prostate cancer than total PSA and they also may preferentially detect the more aggressive forms of the disease.

Materials And Methods: Research immunoassays with high specificity for pro-PSA forms were used to study 1091 retrospective serum specimens, including 555 with 2 to 4 and 536 with 4 to 10 ng/ml PSA, from men enrolled in prostate cancer screening studies who underwent prostate biopsy.

Results: In the 2 to 4 ng/ml PSA range the ratio of pro- to free-PSA (percent pro-PSA) using a cutoff of 1.

Proenzyme forms of prostate-specific antigen in serum improve the detection of prostate cancer.

Introduction: Pro or precursor forms of prostate-specific antigen (PSA) have emerged as potentially important diagnostic serum markers for prostate cancer detection. Immunoassays were developed to measure specific proPSA forms containing propeptides of 2, 4, and 7 amino acids [(-2)proPSA, (-4)proPSA, and (-7)proPSA, respectively].

Methods: Research-use dual monoclonal antibody immunoassays using europium-labeled detection monoclonal antibodies were developed for each form of proPSA.

Volume-based evaluation of serum assays for new prostate-specific antigen isoforms in the detection of prostate cancer.

Objectives: Recently, disease-specific isoforms of the prostate-specific antigen (PSA) have been identified. We evaluated the efficacy of precursor isoforms of PSA (pPSA) and an internally cleaved form of PSA referred to as the benign prostatic hyperplasia-associated PSA (BPSA) for the detection of prostate cancer.

Methods: Serum concentrations of [-2], [-4], and [-7]pPSA, sum pPSA ([-2] + [-4] + [-7]pPSA), and BPSA were retrospectively measured in 43 selected men.

Serum pro prostate specific antigen improves cancer detection compared to free and complexed prostate specific antigen in men with prostate specific antigen 2 to 4 ng/ml.

Purpose: Pro prostate specific antigen (pPSA) is a precursor form of PSA enriched in tumor compared to benign prostate tissues that may be a more specific serum marker for prostate cancer. Serum pPSA was measured in the clinically relevant early detection PSA range of 2 to 10 ng/ml.

Materials And Methods: Research use immunoassays were used to measure native and truncated forms of pPSA.

Evaluation of proprostate specific antigen for early detection of prostate cancer in men with a total prostate specific antigen range of 4.0 to 10.0 ng/ml.

Purpose: In contemporary screening populations a major drawback of prostate specific antigen (PSA) is its relative lack of specificity, especially in the range of 4 to 10 ng/ml, where prostate cancer is found 25% of the time. ProPSA is a derivative of free PSA (fPSA) consisting of the truncated forms (eg [-2]proPSA, [-4]proPSA or the full-length [-7]proPSA). There is increasing evidence that proPSA is associated preferentially with prostate cancer.

Pro PSA: a more cancer specific form of prostate specific antigen for the early detection of prostate cancer.

BPSA and proPSA are distinct molecular forms of free PSA in serum. BPSA is a form of free PSA that is associated with BPH. The inactive precursor of PSA, proPSA, is associated with prostate tumors.

Immunohistochemical staining of prostate cancer with monoclonal antibodies to the precursor of prostate-specific antigen.

Objectives: To characterize the immunohistochemical staining (IHS) of precursor forms of prostate-specific antigen (pro-PSA) forms in prostate cancer, high-grade prostatic intraepithelial neoplasia (HGPIN), and benign tissue from the peripheral and transition zones. Pro-PSA have previously been shown to be more concentrated in prostate cancer tissue extracts than in benign tissue.

Methods: Prostate needle biopsies showing HGPIN (22 sections, 11 patients) and adenocarcinoma (30 sections, 21 patients) and 17 radical prostatectomy and 3 open prostatectomy specimens were identified from the surgical pathology files of Johns Hopkins Hospital.

Standardization of two immunoassays for human glandular kallikrein 2.

Background: Measurement of human kallikrein 2 (hK2) has improved early detection and staging of prostate cancer. However, reported concentrations of hK2 among currently used assays have not been standardized in any way. We compared two hK2 assays and five different recombinant hK2 variants (rhK2) and suggest a common calibrator as an important step and putative reference substance in hK2 assay standardization.

Proenzyme psa for the early detection of prostate cancer in the 2.5-4.0 ng/ml total psa range: preliminary analysis.

Objectives: To determine the clinical utility of using proenzyme prostate-specific antigen (pPSA) for early detection of prostate cancer in the 2.5 to 4.0 ng/mL total PSA range.

Benign prostate-specific antigen (BPSA) in serum is increased in benign prostate disease.

Background: BPSA is a "benign" form of free prostate-specific antigen (PSA) that is increased in prostate transition zone tissues of men with pathologic benign prostatic hyperplasia (BPH). We developed an immunoassay to determine the concentration of BPSA in the serum of men with BPH.

Methods: The BPSA antigen was purified by HPLC, and murine monoclonal antibodies were prepared by standard methods.