Kwiatkowski M K, Recker F, Piironen T, Pettersson K, Otto T, Wernli M, Tscholl R
Clinic of Urology, Kantonsspital Aarau, Switzerland.
Urology. 1998 Sep;52(3):360-5. doi: 10.1016/s0090-4295(98)00245-3.
Human glandular kallikrein (hK2) possesses approximately 80% structure identity with prostate-specific antigen (PSA). Moreover, messenger ribonucleic acid for hK2 and for PSA is expressed in both benign and malignant prostatic tissue. We investigated whether the hK2 serum measurement may improve the detection of prostate cancer (PCa) in patients with total PSA of 4 to 10 ng/mL (diagnostic "gray zone").
Blood samples were obtained from 90 consecutive male patients with lower urinary tract symptoms and total PSA values of 4 to 10 ng/mL. Eighty-one patients underwent transurethral resection of the prostate and 6 radical prostatectomy. The patients were divided into two groups: I, patients with PCa (n = 20) and II, patients with benign prostatic hyperplasia (BPH) (n = 70). An "in-house" immunofluorometric assay with analytical sensitivity of 0.01 ng/mL and the functional sensitivity of 0.05 ng/mL (at this level the mean coefficient of variation, calculated from the precision profile based on the assays of serum samples, was less than 20%) was used to determine serum hK2 concentrations. Total PSA, free PSA (ProStatus), and PSA complexed to alpha1-antichymotrypsin (PSA-ACT) were also measured. Free/total PSA, hK2/total PSA, and hK2/free PSA ratios were calculated.
The serum hK2 could be detected in all samples and in 76 (84.4%) of 90 samples (PCa, n = 18; BPH, n = 58) at given functional sensitivity level. For these cases the median concentration of hK2 was 0.135 ng/mL in PCa and 0.09 ng/mL in BPH (P < 0.1). The median hK2/total PSA ratio was 2% for PCa and 1.6% for BPH (P < 0.2). The median free/total PSA ratio was 0.122 for PCa and 0.215 for BPH (P < 0.0008) and the hK2/free PSA ratio was 0.139 for PCa and 0.075 for BPH (P < 0.000003). At a 7.2% cutoff, the specificity of hK2/free PSA ratio was 48.2% at 100% sensitivity and increased to 60.3% at 94.4% sensitivity level (the area under the receiver operating characteristic curve was 0.86). In comparison, the free/total PSA ratio at a 25.2% cutoff had a sensitivity of 94.4% and a specificity of 27.6% (area under the curve = 0.76).
hK2 was detected in all sera with total PSA values of 4 to 10 ng/mL. Of particular clinical interest is the finding that the hK2/free PSA ratio had a better specificity without loss of sensitivity for PCa than total PSA or the PSA free/total ratio within the range of 4 to 10 ng/mL total PSA. hK2 in combination with free PSA may offer a new diagnostic means for PCa detection.
人腺激肽释放酶（hK2）与前列腺特异性抗原（PSA）具有约80%的结构同一性。此外，hK2和PSA的信使核糖核酸在良性和恶性前列腺组织中均有表达。我们研究了检测血清hK2是否能改善总PSA在4至10 ng/mL（诊断“灰色区”）的患者中前列腺癌（PCa）的检测。
从90例连续的有下尿路症状且总PSA值为4至10 ng/mL的男性患者中采集血样。81例患者接受了经尿道前列腺切除术，6例接受了根治性前列腺切除术。患者被分为两组：I组，PCa患者（n = 20）；II组，良性前列腺增生（BPH）患者（n = 70）。采用一种“内部”免疫荧光测定法，分析灵敏度为0.01 ng/mL，功能灵敏度为0.05 ng/mL（在此水平，根据血清样本检测的精密度曲线计算的平均变异系数小于20%）来测定血清hK2浓度。还检测了总PSA、游离PSA（ProStatus）以及与α1-抗糜蛋白酶结合的PSA（PSA-ACT）。计算游离/总PSA、hK2/总PSA以及hK2/游离PSA比值。
在给定的功能灵敏度水平下，所有样本以及90个样本中的76个（84.4%）（PCa组18个；BPH组58个）均可检测到血清hK2。对于这些病例，PCa组hK2的中位浓度为0.135 ng/mL，BPH组为0.09 ng/mL（P < 0.1）。PCa组hK2/总PSA比值的中位数为2%，BPH组为1.6%（P < 0.2）。PCa组游离/总PSA比值的中位数为0.122，BPH组为0.215（P < 0.0008），hK2/游离PSA比值PCa组为0.139，BPH组为0.075（P < 0.000003）。在7.2%的临界值时，hK2/游离PSA比值在100%灵敏度下的特异性为48.2%，在94.4%灵敏度水平时增至60.3%（受试者操作特征曲线下面积为0.86）。相比之下，在25.2%的临界值时，游离/总PSA比值的灵敏度为94.4%，特异性为27.6%（曲线下面积 = 0.76）。
在所有总PSA值为4至10 ng/mL的血清中均检测到了hK2。特别具有临床意义的是，发现在总PSA为4至10 ng/mL范围内，hK2/游离PSA比值对PCa的特异性优于总PSA或游离/总PSA比值，且不失灵敏度。hK2与游离PSA联合使用可能为PCa检测提供一种新的诊断方法。
