Molecular Heterogeneity of Free PSA in Sera of Patients with Benign and Malignant Prostate Tumors

Hilz, Helmuth; Noldus, Joachim; Hammerer, Peter; Buck, Fritz; Lück, Martina; Huland, Hartwig

doi:10.1159/000020006

Cited by 38 publications

(28 citation statements)

References 18 publications

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“…The understanding of these tissue forms of PSA is important because any PSA in the blood is thought to derive from the tissues. It is interesting that Western blot studies of free PSA forms in BPH serum suggest that BPH serum can contain significant quantities of a 29-kDa form of PSA consistent with PSA 182(ϩ) (24 ). The BPSA assay described in the present study measures both BPSA and PSA 182(ϩ) equally.…”

Section: Discussionmentioning

confidence: 71%

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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Section: Discussionmentioning

confidence: 71%

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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“…In this study, we preferred a conventional polyclonal antibody to a monoclonal antibody because polyclonal antibodies generally recognize not only mature PSA but also a wide range of cleaved PSA forms (21 ). One limitation of the 2DE method used in this study should be considered, similar to that of the procedures described above (11,12,22 ), i.e., PSA not covalently bound to proteins could appear as fPSA forms. However, only a negligible error is likely because very little PSA is bound in such a way, e.g., to inter-␣-trypsin inhibitor (8 ).…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

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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“…These results were then confirmed with overlapping nonapeptides offset by one. This linear epitope was located just before the major PSA cleavage site detected in sera (K145/K146) [15,16]. The epitope sequence is not affected by subsequent cleavages [17] and may even be more accessible on PSA cleaved at residues K145/K146.…”

Section: Characterization Of the Anti-psa 13c9e9d6g8 Antibody Epitopementioning

confidence: 99%

Differential diagnosis of prostate cancer and benign prostate hyperplasia using two-dimensional electrophoresis

et al. 2001

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Prostate specific antigen (PSA) is a protease which is characteristic of the prostate. It is widely used as a serum marker for the early diagnosis of prostate cancer (PCa). Nevertheless, for concentrations between 4 and 10 ng/mL, PSA does not enable PCa to be distinguished from benign diseases, such as benign prostate hyperplasia (BPH). In sera, the use of a ratio between free PSA (PSA uncomplexed with protease inhibitor) and total PSA (free PSA and PSA bound to alpha-1 anti-chymotrypsin) enables the "gray zone" to be reduced, but an important proportion of patients are still wrongly classed. Using two-dimensional electrophoresis, we demonstrated using 52 PCa and 40 BPH well-documented clinical cases that BPH sera show a significantly greater percentage of low-molecular-weight free PSA elements (IwPSA) than PCa sera. In our study, the use of a ratio between IwPSA and standard free PSA enables the correct diagnosis of 100% of PCa and 82.5% of BPH cases as against when 73.1% and 42.5% respectively were correctly diagnozed using the total PSA and the free/total PSA ratio. This important finding may be related to differences in the mechanism secreting PSA from the prostate into the bloodstream. We have shown how a tissue marker may be turned into a powerful tumor marker by events probably unrelated to its expression.

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Molecular Heterogeneity of Free PSA in Sera of Patients with Benign and Malignant Prostate Tumors

Cited by 38 publications

References 18 publications

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

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

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

Differential diagnosis of prostate cancer and benign prostate hyperplasia using two-dimensional electrophoresis

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