A precursor form of PSA (pPSA) is a component of the free PSA in prostate cancer serum

Mikolajczyk, Stephen D.; Grauer, Lana S.; Millar, Lisa S.; Hill, Timothy M.; Kumar, Abhay; Rittenhouse, Harry G.; Wolfert, Robert L.; Saedi, Mohammad S.

doi:10.1016/s0090-4295(97)00449-4

Cited by 137 publications

(65 citation statements)

References 15 publications

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“…Interestingly, patients with BPH have an increased ratio of serum fPSA, which is the basis for the use of %fPSA in the detection of PCa. The free forms of PSA may include mature, inactive PSA and various forms of inactivated PSA as well as precursor forms of PSA such as p2PSA [22]. A previous paper [23] demonstrated that the truncated isoforms of p2PSA were elevated in the peripheral zone of the prostate; in contrast, little or no p2PSA was found in the transition zone, the site of pathological BPH commonly related to prostatic enlargement and finally to PV.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Prostate-Specific Antigen Isoform p2PSA and Its Derivates, %p2PSA, Prostate Health Index and Prostate Dimension-Adjusted Related Index in the Detection of Prostate Cancer at First Biopsy: An Exploratory, Prospective Study

Mearini¹,

Ferri

Lazzeri

et al. 2014

Urol Int

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Objective: To confirm the accuracy of serum proPSA (p2PSA) and its derivatives, percentage of p2PSA to free PSA (%p2PSA) and Prostate Health Index (PHI) and to test the value of prostate dimension-adjusted related index p2PSA density (p2PSAD), %p2PSA density (%p2PSAD) and PHI density (PHID) in discriminating between patients with and without prostate cancer (PCa). Patients and Methods: This is a prospective cohort study of 275 patients with a total PSA (tPSA) of 2-10 ng/ml who underwent initial prostate biopsy. Multivariate logistic regression models were complemented by predictive accuracy analysis. Results: PCa was diagnosed in 31.2% of subjects. Median tPSA did not differ between groups, while PSA density (PSAD), percent free PSA (%fPSA), p2PSA, %p2PSA, PHI, p2PSAD, %p2PSAD and PHID (all p < 0.05) were different between men with and without PCa. Univariate accuracy analysis showed p2PSAD (area under the receiver-operating characteristic curve [AUC]: 0.71), %p2PSAD (AUC: 0.76) and PHID (AUC: 0.77) to be the most accurate predictors of PCa at biopsy, significantly outperforming tPSA (AUC: 0.54), PSAD (AUC: 0.68) and %fPSA (AUC: 0.59) (p ≤ 0.001). At multivariate logistic regression models, p2PSAD and PHID signiﬁcantly increased the accuracy of the basal multivariate model (all p < 0.01). At 90% specificity, sensitivity for p2PSAD, %p2PSAD and PHID were 33.7, 43 and 40.7%, respectively. Spearman's rho coefficient analysis demonstrated a significant relationship between Gleason score, %p2PSA (r = 0.216, p = 0.046), PHI (r = 0.223, p = 0.039) and %p2PSAD (r = 0.205, p = 0.05). Conclusions: Considering patients suited for initial prostate biopsy by a tPSA range of 2-10 ng/ml, PSA isoforms were confirmed to be strong predictors of PCa. The prostate dimension-adjusted PSA isoforms have been shown to differentiate between patients with or without PCa, with an AUC of 0.71-0.77, p2PSAD offering a gain in accuracy with respect to tPSA, %fPSA and PSAD.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Prostate-Specific Antigen Isoform p2PSA and Its Derivates, %p2PSA, Prostate Health Index and Prostate Dimension-Adjusted Related Index in the Detection of Prostate Cancer at First Biopsy: An Exploratory, Prospective Study

Mearini¹,

Ferri

Lazzeri

et al. 2014

Urol Int

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“…The exact reason for this phenomenon has not been elucidated, but it has been shown that the fPSA fraction is heterogeneous (11,12 ). The so-called fPSA subforms proPSA, BPH-associated PSA, and intact PSA have been characterized in detail and recommended for diagnostic purposes (13)(14)(15)(16)(17)(18)(19)(20). However, an even larger number of PSA subforms could be separated as specific spots by two-dimensional electrophoresis (2DE) and immunoblotting (11,21 ).…”

mentioning

confidence: 99%

Analysis of Subforms of Free Prostate-Specific Antigen in Serum by Two-Dimensional Gel Electrophoresis: Potential to Improve Diagnosis of Prostate Cancer

Jung

Reiche²,

Boehme³

et al. 2004

Clinical Chemistry

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Background:The aim of this study was to develop a method to separate and quantify subforms of free prostate-specific antigen (fPSA) in serum by two-dimensional electrophoresis and to assess the diagnostic accuracy of these subforms for prostate cancer (PCa) diagnosis in comparison with total PSA (tPSA) and the ratio of fPSA to tPSA (%fPSA). Methods: Sera from 50 patients with and without PCa, respectively, were studied. PSA was isolated by immunoadsorption on streptavidin-coated magnetic beads with biotinylated anti-PSA antibodies and separated by two-dimensional electrophoresis. After semidry blotting, the intensities of the fPSA spots were quantified by chemiluminescence using an imager analyzer. Results: The method detected subforms to a concentration of 0.1 g/L fPSA with an imprecision (CV) <16%. We detected 15 immunoreactive fPSA spots of different intensities. Spots F2 and F3 were present in all samples. F2 was lower in samples from non-PCa patients (median, 23%) than in samples from PCa patients (49%), whereas F3 behaved inversely (non-PCa, 73%; PCa, 45%). Ratios of F2 to F3 and F2/F3 to %fPSA, respectively, showed improved diagnostic accuracy compared with tPSA and %fPSA. Better differentiation by F2/F3 or

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“…Although each of these inactive PSA forms may also be present in the serum at some concentration, the major percentage of free (noncomplexed) PSA in serum is now known to comprise at least three distinct forms of inactive PSA, which have been recently reviewed (10 ). This includes one form of PSA that has been identified as the proenzyme, or precursor form of PSA (pPSA), which is associated with cancer (11)(12)(13)(14). A second PSA form appears to be composed largely of intact PSA that is similar to native, active PSA except that it is enzymatically inactive (15)(16)(17).…”

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confidence: 99%

Benign Prostate-specific Antigen (BPSA) in Serum Is Increased in Benign Prostate Disease

Linton¹,

Marks

Millar³

et al. 2003

Clinical Chemistry

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Background: BPSA is a "benign" form of free prostatespecific 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 g/L had a median of 0.22 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 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.

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A precursor form of PSA (pPSA) is a component of the free PSA in prostate cancer serum

Cited by 137 publications

References 15 publications

Evaluation of Prostate-Specific Antigen Isoform p2PSA and Its Derivates, %p2PSA, Prostate Health Index and Prostate Dimension-Adjusted Related Index in the Detection of Prostate Cancer at First Biopsy: An Exploratory, Prospective Study

Evaluation of Prostate-Specific Antigen Isoform p2PSA and Its Derivates, %p2PSA, Prostate Health Index and Prostate Dimension-Adjusted Related Index in the Detection of Prostate Cancer at First Biopsy: An Exploratory, Prospective Study

Analysis of Subforms of Free Prostate-Specific Antigen in Serum by Two-Dimensional Gel Electrophoresis: Potential to Improve Diagnosis of Prostate Cancer

Benign Prostate-specific Antigen (BPSA) in Serum Is Increased in Benign Prostate Disease

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