Elsevier

Urology

Volume 56, Issue 2, August 2000, Pages 267-272
Urology

Adult urology
Determination of prostate-specific antigen complexed to alpha2-macroglobulin in serum increases the specificity of free to total PSA for prostate cancer

https://doi.org/10.1016/S0090-4295(00)00609-9Get rights and content

Abstract

Objectives. To determine whether prostate-specific antigen (PSA) complexed to alpha2-macroglobulin (A2M) increases the specificity of free PSA (fPSA) and total PSA (tPSA) for the diagnosis of prostate cancer (PCa).

Methods. In a series of 73 patients with PCa and 58 with benign prostatic hyperplasia (BPH), fPSA, tPSA, and PSA complexed with A2M (PSA-A2M) in serum were determined by specific immunoassays. The assay for PSA-A2M was based on the immunoadsorption of immunoreactive PSA in serum and the measurement of the PSA immunoreactivity released by denaturation of PSA-A2M at pH 11.4.

Results. The median proportion of PSA-A2M [ %PSA-A2M=PSA-A2M/(tPSA+PSA-A2M)] and that of fPSA ( %fPSA=fPSA/tPSA) were significantly lower in patients with PCa (8.2% and 12.4%, respectively) than in patients with BPH (11.6% and 22.5%, P = 0.0014 and P <0.0001, respectively). The median sum of %PSA-A2M and %fPSA was 22.4% in PCa and 38.2% in BPH (P <0.0001). When the sum of %PSA-A2M and %fPSA was used as a diagnostic test for PCa, 57% of patients with “falsely” elevated PSA concentrations (4 to 10 ng/mL) caused by BPH could be correctly identified without missing patients with PCa compared with 18% of the patients with BPH but not PCa using %fPSA alone.

Conclusions. Measurement of the sum of %PSA-A2M and %fPSA in serum significantly improves the cancer specificity of the PSA test compared with the use of tPSA and %fPSA.

Section snippets

Patients

Samples were obtained from consecutive patients referred to the Department of Urology, Helsinki University Central Hospital during May 1995 to October 1996. The study comprised 73 patients with PCa (median age 68 years, range 50 to 96) and 58 with BPH (median age 70 years, range 52 to 82, P >0.05). All patients with PCa for whom pretreatment serum samples were available were included. To minimize the risk of undetected PCa in the patients with BPH, we included only patients with BPH who had

Results

The concentrations of tPSA ranged from 0.4 to 432.5 ng/mL (median 13.5, Table I) in serum from patients with PCa and 1 to 73 ng/mL (median 4.9) in those with BPH (P <0.0001). The %PSA-A2M in serum was also lower (8.2%) in PCa than in BPH (11.6%, P = 0.0014). When only sera with tPSA concentrations in the range of 4 to 10 ng/mL were analyzed, the median %PSA-A2M was also significantly lower in PCa (6.2%) than in BPH (12.4%, P = 0.007). The median %fPSA was also lower in PCa than in BPH (P =

Comment

We have recently developed an assay for PSA-A2M in serum and showed that the ratio of PSA-A2M to tPSA is lower in patients with PCa than in those with BPH.9 Thus, PSA-A2M behaves like fPSA,7, 11 but fPSA and PSA-A2M do not correlate. Therefore, it is possible to further improve the cancer specificity of fPSA and tPSA by using %fPSA and %PSA-A2M in combination with tPSA. In this study, we were able to eliminate more than one half of the false-positive results due to BPH by using the sum of %fPSA

Conclusions

The %PSA-A2M in serum is higher in patients with BPH than in those with PCa, and measurement of the sum of %fPSA and %PSA-A2M significantly reduces the number of false-positive results in BPH obtained with tPSA and %fPSA. These results were obtained in a referred patient population and need to be confirmed in a screening setting. The present method is technically complicated and should be automated to become clinically useful.

Acknowledgements

To Wallac (Turku, Finland) for providing the DELFIA Prostatus PSA Free/Total and EQM kits.

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    This work was supported by grants from the Academy of Finland, the Sigrid Jusélius Foundation, the Finnish Cancer Society, Helsinki University Central Hospital, and the Centre for International Mobility in Finland.

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