Determination of prostate-specific antigen complexed to alpha(2)-macroglobulin in serum increases the specificity of free to total PSA for prostate cancer.
OBJECTIVE
To determine whether prostate-specific antigen (PSA) complexed to alpha(2)-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.
Department of Clinical Chemistry, Helsinki University Central Hospital, Helsinki, Finland.
W M
WM
Zhang
P
P
Finne
J
J
Leinonen
J
J
Salo
U H
UH
Stenman
D000368:Aged; D000818:Animals; D003937:Diagnosis, Differential; D005189:False Positive Reactions; D006801:Humans; D007118:Immunoassay / Q000592:standards; D046911:Macromolecular Substances; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000032:analysis / Q000097:blood*; D011470:Prostatic Hyperplasia / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D011471:Prostatic Neoplasms / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D012680:Sensitivity and Specificity; D000511:alpha-Macroglobulins / Q000032:analysis* / Q000737:chemistry
D046911:Macromolecular Substances; D000511:alpha-Macroglobulins; D017430:Prostate-Specific Antigen