PubMed Health⌕ Search

Biomedical subjects

Stephen D Mikolajczyk

Publications and source records attributed to Stephen D Mikolajczyk.

At least 19 recordsLinked to original sources
PubMed2006

Human tissue kallikrein 5 is a member of a proteolytic cascade pathway involved in seminal clot liquefaction and potentially in prostate cancer progression.

Human tissue kallikreins (hKs) are a family of fifteen serine proteases. Several lines of evidence suggest that hKs participate in proteolytic cascade pathways. Human kallikrein 5 (hK5) has trypsin-like activity, is able to self-activate, and is co-expressed in various tissues with other hKs. In this study, we examined the ability of hK5 to activate other hKs. By using synthetic heptapeptides that encompass the activation site of each kallikrein and recombinant pro-hKs, we demonstrated that hK5 is able to activate pro-hK2 and pro-hK3. We then showed that, following their activation, hK5 can internally cleave and deactivate hK2 and hK3. Given the predominant expression of hK2 and hK3 in the prostate, we examined the pathophysiological role of hK5 in this tissue. We studied the regulation of hK5 activity by cations (Zn2+, Ca2+, Mg2+, Na2+, and K+) and citrate and showed that Zn can efficiently inhibit hK5 activity at levels well below its normal concentration in the prostate. We also show that hK5 can degrade semenogelins I and II, the major components of the seminal clot. Semenogelins can reverse the inhibition of hK5 by Zn2+, providing a novel regulatory mechanism of its serine protease activity. hK5 is also able to internally cleave insulin-like growth factor-binding proteins 1, 2, 3, 4, and 5, but not 6, suggesting that it might be involved in prostate cancer progression through growth factor regulation. Our results uncover a kallikrein proteolytic cascade pathway in the prostate that participates in seminal clot liquefaction and probably in prostate cancer progression.

Blood Coagulation↗
PubMed2006

Prostate-specific antigen test in diagnostic evaluation of chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVES: To determine whether prostate-specific antigen (PSA), the percent free PSA, or free PSA isoforms may be used as diagnostic markers for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS; National Institutes of Health category IIIa and IIIb). METHODS: We evaluated 421 patients enrolled in the Chronic Prostatitis Cohort Study and 112 age-matched controls. Subjects were stratified by the number of white blood cells (WBCs) in their expressed prostatic secretions and pain as determined by the National Institutes of Health Chronic Prostatitis Symptom Index. RESULTS: Total PSA, free PSA, and [-2]proPSA ([-2]pPSA) were significantly elevated in those with CP/CPPS compared with controls (mean PSA 1.97 ng/mL versus 1.72 ng/mL, P = 0.03; mean free PSA 0.76 ng/mL versus 0.70 ng/mL, P = 0.01; and [-2]pPSA 2.38 ng/mL versus 1.80 ng/mL, P = 0.04). The percent free PSA was not significantly different between the patients and controls. For those with CP/CPPS, the percent free PSA was significantly lower as the WBC count rose in the expressed prostatic secretions (0 WBCs = 43.29 versus more than 25 WBCs = 26.52; P < .0001). A PSA level of 4.0 ng/mL or greater was found in 10% of patients and 7% of controls (P = 0.03). CONCLUSIONS: Men with elevated PSA values and CP/CPPS should be treated as one would any other patient screened for prostate cancer with an elevated PSA level. Although PSA, free PSA, and [-2]pPSA were slightly elevated in men with CP/CPPS, the low sensitivity and specificity do not warrant using them as biomarkers for CP/CPPS.

Biomarkers↗
PubMed2006

Alterations in nuclear structure and expression of proPSA predict differences between native Japanese and Japanese-American prostate cancer.

OBJECTIVES: To differentiate the benign and/or malignant epithelial cells in prostate cancer (PCa) glands of native Japanese (NJ) and Japanese-American (JA) men using biomarkers. METHODS: Tissue microarrays from radical prostatectomy specimens of cancerous and adjacent benign areas from 25 NJ and 25 JA prostate glands were studied. Image analysis was used to quantify total prostate-specific antigen (PSA) and proPSA immunohistochemical staining, as well as the variance of several morphometric features from Feulgen-stained epithelial cell nuclei. Logistic regression analysis was applied to determine whether quantitative nuclear grade (QNG) calculations and PSA immunohistochemical staining could differentiate the two test groups. RESULTS: The QNG model differentiated changes in the benign epithelium of the two Japanese groups with an area under the receiver operating characteristic curve of 84% and accuracy of 82% (P = 0.0001). A second QNG model differentiated changes in the malignant epithelium of the two groups with an area under the receiver operating characteristic curve of 84% and accuracy of 76% (P = 0.0023). Logistic regression models combining proPSA immunohistochemical data and QNG from either benign or malignant tissue components yielded areas under the receiver operating characteristic curve of 96% and 91% (P <0.0001) for differentiation of the JA and NJ groups, respectively. CONCLUSIONS: Unique nuclear morphometric alterations demonstrated by QNG combined with proPSA immunohistologic localization independently predicted for significant differences between NJ and JA men with PCa. These preliminary observations indicate a basis for biologic and molecular alterations in the benign adjacent and malignant epithelium between these two groups.

Asian↗
PubMed2006

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. IHS, using monoclonal antibodies against proPSA with a truncated proleader peptide containing 2 amino acids ([-2]pPSA), native ([-5/-7]pPSA), PSA, and PAP, was analyzed. The monoclonal antibodies were specific for both benign and malignant prostatic glandular tissue. IHS with [-5/-7]pPSA showed the least number of cases with negative staining (3%), and the most number of cases with moderate or strong staining (76%). In the 60 cases where all 4 stains could be evaluated, none of them were negative for proPSA and positive for PSA or PAP, and all 7 cases that were negative for both PSA and PAP showed IHS to proPSA. [-5/-7]pPSA (native proPSA) may be a better marker than PSA and PAP in characterizing metastatic prostate adenocarcinoma, with most of the cases showing positivity for the marker. Even cases that were negative for PSA and PAP, were reactive for proPSA. Such enhanced detection is particularly important in poorly differentiated carcinomas involving metastatic sites where prostate carcinoma is a consideration. A panel of markers, including proPSA, should be performed when metastatic prostate carcinoma is in the differential diagnosis.

Acid Phosphatase↗
PubMed2004

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. Sera from patients with prostate cancer or benign prostate disease containing 4-10 microg/L PSA were assayed and analyzed by area under the ROC curve (AUC) for specificity and sensitivity. RESULTS: The proPSA forms had quantification limits of 0.015-0.025 microg/L in serum, with cross-reactivities <1% with PSA. The sum of the proPSA forms divided by free PSA (percentage proPSA) had a higher AUC than did percentage of (-2)proPSA, free PSA, and complexed PSA with AUC (95% confidence intervals) of 0.69 (0.64-0.74), 0.64 (0.58-0.68), 0.63 (0.58-0.68), and 0.57 (0.51-0.62), respectively. The proPSA comprised a median of 33% of the free PSA in cancer and 25% in noncancer sera (P <0.0001). One-third (33%) of cancer samples had >40% proPSA, whereas only 8% of noncancer samples did (P <0.0001). In men with cancer and >25% free PSA, the (-2)proPSA had an AUC of 0.77 (0.66-0.86), with 90% sensitivity and 36% specificity at 0.04 microg/L. CONCLUSIONS: The percentage of proPSA gave better cancer detection in the 4-10 microg/L range than did percentage of free PSA and complexed PSA. (-2)proPSA significantly discriminated cancer in men whose serum had >25% free PSA, for whom there is currently no good marker for cancer detection.

Aged↗
PubMed2004

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. Measurement of these in addition to total PSA significantly increases diagnostic utility. Diagnostic utility is likely to be further increased by adding kallikreins, cytokines, growth factors, receptors and cellular adhesion factors to the biomarker panel. The need for multiple markers reflects the multidimensional nature of prostate disease which ranges from metastatic cancer to indolent cancer to benign hyperplasia and inflammation, all of which require distinct treatments and medical interventions.

Biomarkers, Tumor↗
PubMed2004

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. The median total PSA levels in men with and without cancer were 6.5 microg/L (range 0.4 to 12.1 microg/L) and 6.1 microg/L (range 3.7 to 21.5 microg/L), respectively. Of the 43 men, 15 had clinical T2 prostate cancer with an ultrasound-estimated prostate volume (PV) of greater than 50 mL, 13 had clinical T2 prostate cancer with PV less than 25 mL, and 15 were prostate cancer free with PV greater than 50 mL. RESULTS: The median values for BPSA, free-to-total PSA ratio (f/tPSA), and benign-to-total PSA ratio (B/tPSA) differed statistically between men with cancer and a PV less than 25 mL and men with cancer and a PV greater than 50 mL (P <0.05) and between the men with cancer and a PV less than 25 mL and men without cancer and a PV greater than 50 mL (P <0.005). All evaluated variables had no correlation with tumor volume in 15 men who had undergone radical prostatectomy. CONCLUSIONS: In this preliminary study, the level of [-2], [-4], sum pPSA, and BPSA seemed to be PV related, but only BPSA and B/tPSA and f/tPSA were significantly associated with PV. Therefore, pPSA did not aid in better discriminating cancer from noncancer.

Adenocarcinoma↗
PubMed2004

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. RESULTS: BPSA and free PSA showed stronger correlations with both age (BPSA = 0.38, free PSA = 0.40, PSA = 0.24) and TZ volume (BPSA = 0.67, free PSA = 0.64, PSA = 0.55) than did PSA. The percent free PSA had no statistically significant correlation with TZ volume (P = 0.08). Subtraction of BPSA from free PSA reduced its correlation with TZ volume to below that of PSA (from 0.64 to 0.48). Linear regression analyses showed that, unlike PSA, both BPSA and free PSA displayed an age-independent relationship to TZ volume. The receiver operating characteristic curve (for TZ greater than 30 cm3) and binary logistic regression analyses showed that BPSA (area under the curve = 0.844) outperformed both free PSA (area under the curve = 0.799) and PSA (area under the curve = 0.749) in its ability to predict clinically significant TZ enlargement. CONCLUSIONS: In patients without prostate cancer, the serum concentration of BPSA displayed an age-independent, log-linear relationship to TZ volume and was a better predictor of prostatic enlargement than either PSA or free PSA. BPSA may also predict clinical parameters of BPH and is under evaluation as a marker of BPH progression and response to therapy.

Adult↗
PubMed2004

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. METHODS: Archived sera from 161 consecutive men who were prospectively enrolled in our Early Detection Research Network prostate cancer early detection biomarker program with a percent free PSA value of less than 15% were included in the study. Total PSA, free PSA, proPSA, and BPSA were measured for each sample. RESULTS: The mean total PSA was 6.1 ng/mL (range 1.8 to 24.0). The mean age of the study group was 62 +/- 7 years. Prostate cancer was detected in 66 (41%) of 161 men. The area under the curve-receiver operating characteristic for total and percent free PSA was 0.51 and 0.54, respectively. BPSA and proPSA/BPSA both improved cancer detection compared with percent free PSA alone; the improvement was statistically significant (P <0.001) . The area under the curve-receiver operating characteristic for proPSA/BPSA was 0.72, giving a sensitivity and specificity of 90% and 46%, respectively. CONCLUSIONS: The results of our preliminary studies have suggested that the ratio of proPSA and BPSA can distinguish cancer with greater accuracy when the percent free PSA value is very low (less than 15%), and may, therefore, provide better clinical utility in this lower range of percent free PSA.

Aged↗
PubMed2004

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 1.8% for recommending prostate biopsy detected 90% of cancers, including 16 of 16 extracapsular tumors and 28 of 29 tumors with a pathology Gleason score of 7 or greater, while avoiding 19% of unnecessary biopsies. Serum percent pro-PSA was significantly increased for Gleason score 7 or greater vs less than 7 (p = 0.0018). In the PSA range of 4 to 10 ng/ml percent pro-PSA had the highest cancer specificity, avoiding 31% of unnecessary biopsies, while detecting 34 of 35 cancers with a pathology Gleason score of 7 or greater and 29 of 31 extracapsular tumors. Neither percent free PSA nor complexed PSA enhanced the detection of aggressive cancers in the 4 to 10 ng/ml PSA range. CONCLUSIONS: Percent pro-PSA was superior to percent free and calculated complexed PSA for the detection of prostate cancer in the PSA range of 2 to 10 ng/ml and it had selectivity for detecting more aggressive cancers, as indicated by Gleason score 7 or greater and/or extracapsular tumor extension.

Aged↗
PubMed2004

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. The inactive precursor of PSA, proPSA, is associated with prostate tumors. We have developed research immunoassays with high sensitivity and specificity for BPSA and proPSA. Each of these PSA forms can range from 0-50% of the free PSA in individual serum samples in the total PSA range of 2-10 ng/ml. Typically, BPSA represents from 20-30% of the free PSA in serum, while proPSA ranges from 30-40% of the free PSA. ProPSA greatly improves the early detection of cancer in men with less than 4 ng/ml total PSA. More importantly, proPSA is more highly associated with aggressive cancers than other PSA forms such as PSA-ACT and free PSA. The BPH-associated BPSA and cancer-associated proPSA forms are complementary and provide improved detection of prostate cancer from benign disease.

Biomarkers, Tumor↗
PubMed2003

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. pPSA, the precursor form of PSA that contains a 7 amino acid leader peptide, and truncated forms such as [-2]pPSA and [-4]pPSA can be measured in serum by research immunoassay. METHODS: Archival serum from 119 men (noncancer, 88; cancer, 31), obtained before biopsy and in the total PSA range of 2.5 to 4.0 ng/mL, were assayed for total PSA, free PSA (fPSA), and pPSA. pPSA was defined as the sum of the [-2], [-4], and [-7] forms, and the percent pPSA (%pPSA) was defined as pPSA/fPSA. RESULTS: pPSA averaged 4.6% +/- 0.4% (SEM) of total PSA and 39.3% +/- 3.5% of fPSA. PSA and %fPSA values were similar between the noncancer and cancer groups, and %pPSA tended to be higher in the cancer group (50.1% +/- 4.4%) compared with the noncancer group (35.5% +/- 6.7%; P = 0.07). Using receiver operating characteristic analysis to assess clinical utility, the area under the curve for %pPSA was 0.688 compared with 0.567 for %fPSA. At a fixed sensitivity of 75%, the specificity was significantly greater for %pPSA at 59% compared with %fPSA at 33% (P <0.0001). CONCLUSIONS: In the 2.5 to 4.0 ng/mL total PSA range, 75% of cancers can potentially be detected with 59% of unnecessary biopsies being spared using %pPSA; use of %fPSA would result in sparing only 33% of unnecessary biopsies. A large prospective clinical trial is needed to confirm these preliminary findings.

Adult↗
PubMed2003

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. IHS was performed on formalin-fixed, paraffin-embedded sections using one monoclonal antibody (mAB) against pro-PSA with a truncated pro-leader peptide containing two amino acids, [-2]pPSA, and a second mAB against native pro-PSA ([-5/-7]pPSA). RESULTS: The mABs were specific for both benign and malignant prostatic glandular tissue and did not stain stromal, vascular, or colonic tissue when present in the specimens. All sections with HGPIN and/or adenocarcinoma showed staining with both mABs. HGPIN was strongly positive in most cases (66.1%). The native pro-PSA mAB showed little differential between cancer and benign glands, and the mAB to the truncated [-2]pPSA stained cancer tissue more strongly than benign tissue. Benign atrophic glands often showed negative or weak/patchy staining. No difference was found in the staining pattern between benign glands in the peripheral zone and transition zone. CONCLUSIONS: This study is the first to demonstrate that mABs to pro-PSA can be used as specific IHS for benign and malignant prostatic tissue. [-2]pPSA appears to be preferentially more concentrated in cancer tissue than in benign glands, correlating with previous tissue extract studies. Unlike previous studies with PSA staining, the IHS for pro-PSA remained uniform among the different tumor grades. Therefore, pro-PSA may be a useful marker in differentiating high-grade prostate adenocarcinoma from other non-prostate carcinomas.

Adenocarcinoma↗
PubMed2003

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. The objective of this study was to determine whether proPSA can influence the detection of early prostate cancer. MATERIALS AND METHODS: Archival serum samples obtained from 93 men who underwent a systematic 12-core prostate biopsy (total PSA range 4.0 to 10.0 ng/ml) were assayed for percent free PSA, total PSA and the 3 forms of proPSA (Hybritech Tandem Assays Beckman Coulter Access, Beckman Coulter, Inc., Brea, California). Free PSA, the cumulative sum of individual proPSA forms ([-2], [-4] and [-7], or sum-proPSA) and derivatives were determined. Of the 93 men assessed 41 (44%) had evidence of prostate cancer (76% Gleason 5/6, 19% Gleason 7 and 5% Gleason 8). Prostate volume was measured at systematic 12-core biopsy for the detection of prostate cancer. Results were analyzed using univariate and multivariate logistic regression (LR) nonparametric statistical methods. RESULTS: Using univariate LR, fPSA, percent fPSA (%fPSA), percent sum-proPSA and prostate volume significantly (p <0.05) differentiated men with prostate cancer from those with benign disease. However, applying stepwise backward multivariate LR, total PSA, %fPSA and sum-proPSA were retained and generated a receiver operator characteristic curve with an area under the curve of 76.6%. At 90% sensitivity these 3 variables collectively achieved a specificity of 44% for the detection of prostate cancer. Individually, the 3 retained variables had a specificity of 23% (total PSA), 33% (%fPSA) and 13% (sum-proPSA). CONCLUSIONS: Sum-proPSA, total PSA and %fPSA in combination improve the specificity of early prostate cancer detection in men with a total PSA of 4 to 10 ng/ml compared with the results of individual PSA molecular forms measured.

Adenocarcinoma↗
PubMed2003

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. The subject cohort contained 1,091 serum specimens from men enrolled in prostate cancer screening studies at 2 sites who had undergone prostate biopsy and were divided into PSA ranges of 2 to 4 ng/ml (benign 320, cancer 235) and 4 to 10 ng/ml (benign 315, cancer 221). RESULTS: In PSA ranges 2 to 4, 2 to 6, 4 to 10 and 2 to 10 ng/ml, pPSA in a ratio with free PSA (%pPSA) gave the highest cancer specificity. At 2 to 4 ng/ml and 90% sensitivity, %pPSA spared 19% of unnecessary biopsies compared to 10% for free PSA and 11% for complexed PSA(p <0.001). Similar results were obtained at PSA 2 to 6 ng/ml. At 90% sensitivity in the PSA 4 to 10 ng/ml range, %pPSA spared 31% of unnecessary biopsies compared to 20% for % free PSA and 19% for complexed PSA (p <0.0001). In the combined 2 to 10 ng/ml range, %pPSA spared 21% of unnecessary biopsies compared to 13% for % free PSA and 9% for complexed PSA (p <0.0001). CONCLUSIONS: The %pPSA significantly improved specificity for cancer detection and decreased the number of unnecessary biopsies in the PSA 2 to 4 ng/ml range. This relative improvement of %pPSA compared to % free PSA and complexed PSA was maintained throughout the PSA range of 2 to 10 ng/ml.

Biopsy, Needle↗
PubMed2003

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. A fluorogenic ELISA was developed with high specificity for BPSA and no cross-reactivity with other forms of PSA. RESULTS: The BPSA immunoassay had a lower limit of detection of 6 ng/L and a cross-reactivity of <1% with all other clipped and nonclipped forms of PSA. The BPSA antibody was specific for the internal Lys(182) cleavage site that characterizes BPSA. Biopsy-negative men with a median total PSA of 4.8 micro g/L had a median of 0.22 micro g/L BPSA, representing 25% of the free PSA in serum. BPSA ranged from 0% to 60% of the free PSA in serum. BPSA in a cohort of cancer serum also comprised 25% of the free PSA. Control serum from women or men without increased PSA had nondetectable BPSA. CONCLUSIONS: BPSA is a significant percentage of the free PSA in BPH serum but not in control serum. The presence of prostate cancer does not alter the relative proportions of BPSA in sera with <10 micro g/L PSA. BPSA has a wide distribution of concentrations in the serum and may provide clinical information for the study of men with BPH.

Adult↗
PubMed2003

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. ProPSA is comprised of native proPSA as well as truncated proPSA forms, [-2]pPSA and [-4]pPSA, which have been shown to be more cancer-associated than native proPSA. We have developed highly specific and sensitive research immunoassays for BPSA, and the different forms of proPSA. Free PSA in prostate cancer serum contains a median of 28% BPSA and 32% proPSA, though each form of PSA can range from 0 to more than 50% in individual samples. Early studies revealed that proPSA significantly increases the specificity for prostate cancer, especially in the 2-4 ng/ml PSA range. It is estimated that 20-30% of men with PSA values from 2-4 ng/ml have prostate cancer. In the 2.5-4 ng/ml PSA range proPSA gave a receiver operating characteristic-area under the curve (ROC-AUC) of 0.636 compared with free PSA (0.506) and complex PSA (0.509). At 90% sensitivity the specificity for proPSA was 25% compared to 10% for %FPSA and cPSA (P = < 0.001). ProPSA was superior to %FPSA and complexed PSA in the 4-10 ng/ml PSA range (AUC = 0.689, 0.637 and 0.538, respectively). ProPSA represents a more cancer-specific form of PSA that better discriminates prostate cancer from BPH.

Diagnosis, Differential↗