Clinical Chemistry
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Clinical Chemistry 45: 2040-2041, 1999;
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(Clinical Chemistry. 1999;45:2040-2041.)
© 1999 American Association for Clinical Chemistry, Inc.


Letters

Complexed Prostate-specific Antigen and the "Prostate-specific Antigen Gap"

Bernard L. Croal1,a, Ian Mitchell2, Arthur Dickie1, Patrica A. Duff1, Nicholas P. Cohen2 and Iain S. Ross1

Departments of
1 Clinical Biochemistry, and
2 Urology, Grampian University Hospitals Trust, Aberdeen AB25 2ZD, United Kingdom
a Author for correspondence. Fax 011-44-01224-694378; e-mail b.l.croal{at}abdn.ac.uk


To the Editor:

Jung et al. (1) reported an apparent gap between total serum prostate-specific antigen (t-PSA) and the sum of free PSA (f-PSA) plus {alpha}1-antichymotrypsin-PSA (ACT-PSA) in patients with prostate carcinoma (PCa) but not in those with benign prostatic hypertrophy (BPH). The gap may be attributable to a variety of technical artifacts such as different recognition of multiple forms of f-PSA or t-PSA in the two groups of patients or the lack of equimolarity of the tests used (1). Of more interest, however, is the suggestion by the authors that the appearance of this "PSA gap" reflects an increase in minor PSA complexes in PCa patients that their assay for ACT-PSA does not detect. Indeed, they suggest that such an observation contradicts the high expectations (2) for the determination of ACT-PSA or the ratio of ACT-PSA to t-PSA to improve the differentiation between PCa and BPH.

The authors refer to a novel approach to the measurement of complexed forms of PSA (3) as a possible solution to the potential problem of minor PSA forms. This complexed PSA (c-PSA) assay is now available commercially for the Bayer Immuno-1 automated immunochemistry analyzer (Bayer Diagnostics). We recently used this assay along with measurements of t-PSA (Bayer Immuno-1), f-PSA (Abbott IMx; Abbott Diagnostics), and the ratio of f-PSA to t-PSA (Abbott IMx, both assays) on a prospective basis in men referred to a hospital urology clinic with t-PSA measurements between 3.0 and 22.0 µg/L. Of the 79 consecutive patients assessed to date, 21 (27%) were diagnosed with PCa by a combination of clinical presentation, digital rectal examination, prostatic volume, and transrectal ultrasound-guided prostatic biopsy (all patients). We found no gap between t-PSA (Bayer Immuno-1 assay) and the sum of f-PSA (Abbott IMx assay) and c-PSA (Bayer Immuno-1 assay) in patients with PCa or BPH. The sum of f-PSA and c-PSA was 100.6% (SD, 7.6%) of t-PSA in the BPH patients and 100.5% (SD, 6.2%) in the PCa patients.

We believe, therefore, that our data showing the lack of a PSA gap in both PCa and BPH patients, along with the observations of Jung et al. (1), may help solve the conundrum of why ACT-PSA does not perform as well as predicted.


References

  1. Jung K, Brux B, Knabich A, Lein M, Sinha P, Schnorr D, Loening SA. A gap between total prostate-specific antigen and the sum of free prostate-specific antigen plus {alpha}1-antichymotrypsin-prostate-specific antigen in patients with prostate carcinoma but not in those with benign prostate hyperplasia. Clin Chem 1999;45:422-424. [Free Full Text]
  2. Wu JT, Liu GH. Advantages of replacing the total PSA assay with the assay for PSA-{alpha}1-antichymotrypsin complex for the screening and management of prostate cancer. J Clin Lab Anal 1998;12:32-40. [Web of Science][Medline] [Order article via Infotrieve]
  3. Allard WJ, Zhou Z, Yeung KK. Novel immunoassay for the measurement of complexed prostate-specific antigen in serum. Clin Chem 1998;44:1216-1223. [Abstract/Free Full Text]

The authors of the Technical Brief cited above reply:

Klaus Jung3,a

a Author for correspondence. Fax 49-30-2802-1402; e-mail klaus.jung{at}charite.de

Brigitte Brux4
Pranav Sinha4
Michael Lein3
Dietmar Schnorr3
Stefan A. Loening3

Departments of
3 Urology and,
4 Laboratory Medicine, University Hospital Charité, Humboldt University Berlin, Schumannstrasse 20/21, D-10098 Berlin, Germany


To the Editor:

Our observation of a prostate-specific antigen (PSA) gap in the serum of patients with prostate carcinoma (PCa) and the assumption of the increased occurrence of minor PSA forms in serum may explain the better discrimination between PCa and benign prostatic hyperplasia (BPH) patients by the free/total PSA ratio compared with the determination of the {alpha}1-antichymotrypsin-PSA complex or the ratio of {alpha}1-antichymotrypsin-PSA to total PSA that we observed in 112 untreated patients with PCa and in 34 patients with BPH (1). However, as pointed out in that report and in Ref. (2), we cannot exclude all possible technical reasons for the PSA gap discrepancies between BPH and PCa patients (e.g., calibration of the assays, different recognition of the multiple forms of free PSA or total PSA in both groups, or lack of equimolarity), although we paid particular attention to this problem. It should be mentioned that Espana et al. (3), using homemade immunoassays for the determination of total PSA and {alpha}1-antichymotrypsin-PSA, recently found better discrimination with the ratio of {alpha}1-antichymotrypsin-PSA to total PSA than with the ratio of free to total PSA. Therefore, at present, our results and the mentioned contradictory data should only draw the attention of clinical chemists and physicians to the fact that there are possible biological rather than analytical reasons that contradict the high expectations placed on the determination of {alpha}1-antichymotrypsin-PSA (4). It is obvious that both basic experiments and clinical studies are necessary to solve the whole problem. We hope that a recently performed multicenter study using a newly developed {alpha}1-antichymotrypsin-PSA assay with changed architecture may help clarify this issue.


References

  1. Jung K, Brux B, Lein M, Knäbich A, Sinha P, Rudolph B, et al. Determination of {alpha}1-antichymotrypsin-PSA complex in serum does not improve the differentiation between benign prostatic hyperplasia and prostate cancer compared to total PSA and percentage free PSA. Urology 1999;53:1160-1168. [Web of Science][Medline] [Order article via Infotrieve]
  2. Jung K, Brux B, Knäbich A, Lein M, Sinha P, Schnorr D, Loening SA. A gap between total prostate-specific antigen and the sum of free prostate-specific antigen plus {alpha}1-antichymotrypsin-prostate-specific antigen in patients with prostate carcinoma but not in those with benign prostate hyperplasia. Clin Chem 1999;45:422-425.
  3. Espana F, Royo M, Martinez M, Enguidanos MJ, Vera CD, Estelles A, et al. Free and complexed prostate specific antigen in the differentiation of benign prostatic hyperplasia and prostate cancer: studies in serum and plasma samples. J Urol 1998;160:2081-2088. [Web of Science][Medline] [Order article via Infotrieve]
  4. Wu JT, Liu GH. Advantages of replacing the total PSA assay with the assay for PSA-{alpha}1-antichymotrypsin complex for the screening and management of prostate cancer. J Clin Lab Anal 1998;12:32-40.




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