Mikolajczyk S D, Millar L S, Wang T J, Rittenhouse H G, Wolfert R L, Marks L S, Song W, Wheeler T M, Slawin K M
Hybritech Incorporated, San Diego, CA 92196-9006, USA.
Urology. 2000 Jan;55(1):41-5. doi: 10.1016/s0090-4295(99)00372-6.
The biologic mechanism for the increased proportion of noncomplexed ("free") prostate-specific antigen (PSA) found in the serum of patients with benign prostate disease is unknown. We recently reported that most of the PSA found in benign, hyperplastic, and cancerous prostatic tissue is in the free form. To determine whether specific molecular forms of free PSA are associated differentially with normal, hyperplastic, or cancerous prostatic tissue, we have further characterized the free PSA in each type of prostatic tissue.
PSA was purified by immunoaffinity chromatography from matched prostatic tissue samples of peripheral zone cancer (PZ-C), PZ noncancer (PZ-N), and transition zone (TZ) tissue from 10 large-volume (greater than 50 g) and 8 small-volume (less than 25 g) radical prostatectomy specimens. Eight TZ specimens obtained during transurethral resection of the prostate for benign prostatic hyperplasia (BPH) were also analyzed. The different molecular forms of PSA were further resolved by high-performance hydrophobic interaction chromatography. Clipped forms of PSA were identified by N-terminal amino acid sequencing.
More than 99% of the PSA in prostatic tissues was in the free, noncomplexed form. Specimens from the prostate TZ were found to contain elevated levels of an altered form of PSA, which we designated BPSA. Purified BPSA contained a distinctive cleavage at lysine 182. The median percent BPSA (%BPSA) was 11.4 in the TZ of specimens with nodular BPH compared with a %BPSA of 4.1 in the TZ of specimens without nodular BPH (P <0.0014). The median %BPSA levels of the PZ-N and PZ-C tissues ranged from 3.2 to 4.9 and were not significantly different from one another or from the %BPSA level of TZ tissues without nodular BPH.
We have identified a specific molecular form of clipped free PSA, called BPSA, that is increased within the prostatic TZ of patients exhibiting nodular BPH. Higher levels of percent free PSA in serum have been found to correlate strongly with prostate volume, which in turn is closely associated with the progressive enlargement of nodular BPH tissue within the TZ of the prostate. Thus, it is possible that a proportion of the serum percent free PSA found in patients with BPH may be composed of BPSA released into the serum.
良性前列腺疾病患者血清中未结合（“游离”）前列腺特异性抗原（PSA）比例增加的生物学机制尚不清楚。我们最近报道，在良性、增生性和癌性前列腺组织中发现的大多数PSA呈游离形式。为了确定游离PSA的特定分子形式是否与正常、增生或癌性前列腺组织存在差异关联，我们进一步对每种类型前列腺组织中的游离PSA进行了表征。
通过免疫亲和层析从10个大体积（大于50g）和8个小体积（小于25g）根治性前列腺切除标本的外周区癌（PZ-C）、外周区非癌（PZ-N）和移行区（TZ）组织的匹配前列腺组织样本中纯化PSA。还分析了8例经尿道前列腺电切术治疗良性前列腺增生（BPH）时获得的TZ标本。通过高效疏水相互作用色谱进一步分离PSA的不同分子形式。通过N端氨基酸测序鉴定PSA的剪切形式。
前列腺组织中超过99%的PSA呈游离、未结合形式。发现前列腺TZ标本中含有一种改变形式的PSA，其水平升高，我们将其命名为BPSA。纯化的BPSA在赖氨酸182处有一个独特的切割位点。结节性BPH标本的TZ中BPSA的中位数百分比（%BPSA）为11.4，而无结节性BPH标本的TZ中%BPSA为4.1（P<0.0014）。PZ-N和PZ-C组织的%BPSA中位数水平在3.2至4.9之间，彼此之间以及与无结节性BPH的TZ组织的%BPSA水平无显著差异。
我们鉴定出一种特定的剪切游离PSA分子形式，称为BPSA，在表现为结节性BPH的患者前列腺TZ中增加。血清中游离PSA百分比水平较高与前列腺体积密切相关，而前列腺体积又与前列腺TZ内结节性BPH组织的进行性增大密切相关。因此，BPH患者血清中游离PSA百分比的一部分可能由释放到血清中的BPSA组成。
