Department of Urology, Northwestern University, Chicago, Illinois 60611, USA.
J Urol. 2010 Apr;183(4):1355-9. doi: 10.1016/j.juro.2009.12.056. Epub 2010 Feb 19.
Due to the limited specificity of prostate specific antigen for prostate cancer screening, there is an ongoing search for adjunctive biomarkers. Retrospective studies have suggested that an isoform of proenzyme prostate specific antigen called [-2]proenzyme prostate specific antigen may enhance the specificity of prostate specific antigen based screening. We examined the usefulness of this isoform in a prospective prostate cancer screening study.
From a population of 2,034 men undergoing prostate cancer screening we examined the relationship between the measurement of the [-2]isoform of proenzyme prostate specific antigen (p2PSA) and prostate cancer detection. Specifically we compared the usefulness of total prostate specific antigen, the ratio of free-to-total prostate specific antigen, the ratio of p2PSA-to-free prostate specific antigen, and a formula combining prostate specific antigen, free prostate specific antigen and p2PSA (the Beckman Coulter prostate health index or phi) to predict prostate cancer in men from the study undergoing prostate biopsy with a prostate specific antigen of 2.5 to 10 ng/ml and nonsuspicious digital rectal examination.
Despite similar total prostate specific antigen (p = 0.88), percent free prostate specific antigen (p = 0.02) and %p2PSA (p = 0.0006) distinguished between positive and negative biopsy results. On ROC analysis %p2PSA (AUC 0.76) outperformed prostate specific antigen (AUC 0.50) and percent free prostate specific antigen (AUC 0.68) for differentiating between prostate cancer and benign disease. Setting the sensitivity at 88.5%, p2PSA led to a substantial improvement in specificity as well as positive and negative predictive values. The Beckman Coulter prostate health index (AUC 0.77) had the best overall performance characteristics.
This is the first prospective study to our knowledge to demonstrate that p2PSA provides improved discrimination between prostate cancer and benign disease in screened men with a prostate specific antigen of 2.5 to 10 ng/ml and a negative digital rectal examination.
由于前列腺特异性抗原（PSA）对前列腺癌筛查的特异性有限，因此一直在寻找辅助生物标志物。回顾性研究表明，一种称为前列腺特异性抗原前体酶 [-2] 的同工型可能会提高基于 PSA 的筛查的特异性。我们在一项前瞻性前列腺癌筛查研究中检验了这种同工型的实用性。
我们从 2034 名接受前列腺癌筛查的男性中，研究了前体酶前列腺特异性抗原 [-2] 同工型（p2PSA）的测量与前列腺癌检出之间的关系。具体来说，我们比较了总前列腺特异性抗原、游离前列腺特异性抗原与总前列腺特异性抗原的比值、p2PSA 与游离前列腺特异性抗原的比值，以及将前列腺特异性抗原、游离前列腺特异性抗原和 p2PSA 结合在一起的公式（贝克曼库尔特前列腺健康指数或 phi）在总前列腺特异性抗原为 2.5 至 10ng/ml 且直肠指检无异常的研究人群中预测前列腺活检阳性的能力。
尽管总前列腺特异性抗原相似（p=0.88），但游离前列腺特异性抗原百分比（p=0.02）和 %p2PSA（p=0.0006）可区分活检阳性和阴性结果。ROC 分析显示，%p2PSA（AUC 0.76）在区分前列腺癌和良性疾病方面优于前列腺特异性抗原（AUC 0.50）和游离前列腺特异性抗原百分比（AUC 0.68）。当灵敏度设定为 88.5%时，p2PSA 可显著提高特异性以及阳性和阴性预测值。贝克曼库尔特前列腺健康指数（AUC 0.77）具有最佳的整体性能特征。
这是我们所知的第一项前瞻性研究，证明在总前列腺特异性抗原为 2.5 至 10ng/ml 且直肠指检阴性的筛查男性中，p2PSA 可提高前列腺癌与良性疾病之间的区分能力。
