STABILITY OF FREE AND TOTAL PROSTATE-SPECIFIC ANTIGEN IN SERUM FROM PATIENTS WITH PROSTATE CARCINOMA AND BENIGN HYPERPLASIA

Purpose: Instability of prostate specific antigen (PSA) in serum might complicate the interpretation of the free-to-total PSA ratio. We stud ied the in vitro stability of free PSA and total PSA in serum of patie nts with prostate cancer or benign prostate hyperplasia (BPH), and of elderly men without known prostate disease. Furthermore, we investigat ed conditions to stabilize the in vitro values in serum. Materials and Methods: The effects of storage at 4C on free and total PSA were inve stigated in serum of 32 men with prostate cancer, 25 with BPH and 29 o lder than 70 years. All had total PSA less than 25 mu g./l. The influe nce of total PSA levels on in vitro changes in free-to-total PSA was s tudied in serum of 39 other prostate cancer patients (total PSA 1.7 to 298 mu g./l.). Stabilization studies were performed in yet another se ries of samples from 54 prostate cancer patients (total PSA 1.3 to 238 mu g./l.) by adjustment of serum pH to 5.5 before storage. Free and t otal PSA was measured by a commercial immunofluorometric assay, as wel l as by in-house immunofluorometric assays. Statistical analyses of th e results were performed by analysis of variance with repeated measure s. Results: We found no difference between the results obtained by the 2 assay systems. After 7 days at 4C there was a slight decrease in to tal PSA in sera of prostate cancer patients, BPH patients and men olde r than 70 years. A decrease in mean free PSA values occurred in all gr oups (21.3, 15.7 and 14.6%, respectively). The decrease of free PSA wi th time was significant (p < 0.0001) in all groups but there was no si gnificant difference among the groups (p = 0.16). The concomitant decr ease in free-to-total PSA ratio was significant in all groups (p < 0.0 001). This change was group dependent (p = 0.003), with the largest de crease in the prostate cancer group. Large interindividual differences were observed. Storage at 4C for 7 days of sera of 39 patients with l ocalized and disseminated prostate cancer (total PSA 1.7 to 298 mu g./ l,) gave a more pronounced decrease in free PSA than in total PSA. Adj ustment of serum pH to 5.5 had a stabilizing effect on free PSA and on the free-to-total PSA ratio, giving a significantly smaller change in both values (p < 0.0001). Conclusions: In vitro instability of free P SA in serum and large interindividual differences should be considered when using the ratio of free-to-total PSA in evaluation of patients w ith suspected prostate cancer. Serum samples should be stored frozen i f not analyzed immediately or acidified to pH 5.5. Interpretation of d ata from determination of free-to-total PSA ratio should be done with caution if the sampling and storage conditions are not known.