Paus E, Nilsson O, Børmer O P, Fosså S D, Otnes B, Skovlund E
Central Laboratory, Department of Oncology and Clinical Research Office, The Norwegian Radium Hospital, Oslo.
J Urol. 1998 May;159(5):1599-605. doi: 10.1097/00005392-199805000-00051.
Instability of prostate specific antigen (PSA) in serum might complicate the interpretation of the free-to-total PSA ratio. We studied the in vitro stability of free PSA and total PSA in serum of patients with prostate cancer or benign prostate hyperplasia (BPH), and of elderly men without known prostate disease. Furthermore, we investigated conditions to stabilize the in vitro values in serum.
The effects of storage at 4C on free and total PSA were investigated in serum of 32 men with prostate cancer, 25 with BPH and 29 older than 70 years. All had total PSA less than 25 microg./l. The influence of total PSA levels on in vitro changes in free-to-total PSA was studied in serum of 39 other prostate cancer patients (total PSA 1.7 to 298 microg./l.). Stabilization studies were performed in yet another series of samples from 54 prostate cancer patients (total PSA 1.3 to 238 microg./l.) by adjustment of serum pH to 5.5 before storage. Free and total PSA was measured by a commercial immunofluorometric assay, as well as by in-house immunofluorometric assays. Statistical analyses of the results were performed by analysis of variance with repeated measures.
We found no difference between the results obtained by the 2 assay systems. After 7 days at 4C there was a slight decrease in total PSA in sera of prostate cancer patients, BPH patients and men older than 70 years. A decrease in mean free PSA values occurred in all groups (21.3, 15.7 and 14.6%, respectively). The decrease of free PSA with time was significant (p <0.0001) in all groups but there was no significant difference among the groups (p=0.16). The concomitant decrease in free-to-total PSA ratio was significant in all groups (p <0.0001). This change was group dependent (p=0.003), with the largest decrease in the prostate cancer group. Large interindividual differences were observed. Storage at 4C for 7 days of sera of 39 patients with localized and disseminated prostate cancer (total PSA 1.7 to 298 microg./l.) gave a more pronounced decrease in free PSA than in total PSA. Adjustment 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).
In vitro instability of free PSA in serum and large interindividual differences should be considered when using the ratio of free-to-total PSA in evaluation of patients with suspected prostate cancer. Serum samples should be stored frozen if not analyzed immediately or acidified to pH 5.5. Interpretation of data from determination of free-to-total PSA ratio should be done with caution if the sampling and storage conditions are not known.
血清中前列腺特异性抗原（PSA）的不稳定性可能会使游离PSA与总PSA比值的解读变得复杂。我们研究了前列腺癌或良性前列腺增生（BPH）患者以及无已知前列腺疾病的老年男性血清中游离PSA和总PSA的体外稳定性。此外，我们还研究了稳定血清中体外值的条件。
在32例前列腺癌男性、25例BPH男性和29例70岁以上男性的血清中，研究了4℃储存对游离PSA和总PSA的影响。所有患者的总PSA均低于25μg/l。在另外39例前列腺癌患者（总PSA为1.7至298μg/l）的血清中，研究了总PSA水平对游离PSA与总PSA体外变化的影响。通过在储存前将54例前列腺癌患者（总PSA为1.3至238μg/l）的另一系列样本的血清pH值调节至5.5进行稳定性研究。游离PSA和总PSA通过商业免疫荧光测定法以及内部免疫荧光测定法进行测量。结果的统计分析采用重复测量方差分析。
我们发现两种检测系统获得的结果之间没有差异。在4℃下储存7天后，前列腺癌患者、BPH患者和70岁以上男性血清中的总PSA略有下降。所有组的平均游离PSA值均下降（分别为21.3%、15.7%和14.6%）。所有组中游离PSA随时间的下降均具有显著性（p<0.0001），但各组之间无显著差异（p=0.16）。所有组中游离PSA与总PSA比值的相应下降均具有显著性（p<0.0001）。这种变化与组别有关（p=0.003），前列腺癌组下降最大。观察到个体间差异很大。39例局限性和播散性前列腺癌患者（总PSA为1.7至298μg/l）的血清在4℃下储存7天，游离PSA的下降比总PSA更明显。将血清pH值调节至5.5对游离PSA和游离PSA与总PSA比值具有稳定作用，使两者的值变化显著更小（p<0.0001）。
在对疑似前列腺癌患者进行评估时，使用游离PSA与总PSA比值时应考虑血清中游离PSA的体外不稳定性和个体间的巨大差异。如果不立即分析，血清样本应冷冻保存或酸化至pH 5.5。如果采样和储存条件未知，对游离PSA与总PSA比值测定数据的解读应谨慎进行。
