Zellweger Tobias, Ninck Christoph, Mirlacher Martina, Annefeld Matthias, Glass Andrew G, Gasser Thomas C, Mihatsch Michael J, Gelmann Edward P, Bubendorf Lukas
Department of Urology, University of Basel, Schönbeinstrasse 40, 4031 Basel, Switzerland.
Prostate. 2003 Apr 1;55(1):20-9. doi: 10.1002/pros.10209.
Tissue microarrays (TMA) have recently emerged as powerful tools to rapidly analyze the clinical significance of new molecular markers in human tumors. Here, we have tested several molecular markers on a prostate TMA containing 637 different specimens.
The specimens were from 551 patients with prostate cancer and long-term follow-up information on progression (median 5.3 years), tumor-specific and overall survival (median 5.9 years). Eighty-six specimens from benign prostatic hyperplasia were included as controls. Expression of Ki67, Bcl-2, p53, CD-10 (neutral endopeptidase), and syndecan-1 (CD-138) was analyzed by immunohistochemistry.
Gleason grade and Ki67 Labeling Index (LI) were independent predictors of early recurrence and poor survival. Bcl-2 predicted early recurrence, whereas p53 was associated with poor survival. Syndecan-1 overexpression also predicted early recurrence and was significantly associated with tumor specific survival, high Gleason grade, Ki67 LI, and Bcl-2 overexpression. Neoadjuvant hormonal therapy was associated with overexpression of Bcl-2 and inhibition of Ki67 LI and CD-10, but did not affect the expression of the remaining markers.
The results of this TMA study confirm a dominant prognostic significance of Gleason grading and Ki67 LI in prostate cancer, as compared to a less pronounced role of Bcl-2, and p53. We identified syndecan-1 as a new prognostic factor and provide evidence for an androgen-dependent regulation of CD-10 expression.
组织微阵列（TMA）最近已成为快速分析人类肿瘤中新分子标志物临床意义的强大工具。在此，我们在一个包含637个不同标本的前列腺TMA上测试了几种分子标志物。
标本来自551例前列腺癌患者，并具有关于进展（中位时间5.3年）、肿瘤特异性生存和总生存（中位时间5.9年）的长期随访信息。86个来自良性前列腺增生的标本作为对照。通过免疫组织化学分析Ki67、Bcl-2、p53、CD-10（中性内肽酶）和syndecan-1（CD-138）的表达。
Gleason分级和Ki67标记指数（LI）是早期复发和生存不良的独立预测因素。Bcl-2预测早期复发，而p53与生存不良相关。Syndecan-1过表达也预测早期复发，并且与肿瘤特异性生存、高Gleason分级、Ki67 LI和Bcl-2过表达显著相关。新辅助激素治疗与Bcl-2过表达以及Ki67 LI和CD-10的抑制相关，但不影响其余标志物的表达。
这项TMA研究的结果证实，与Bcl-2和p53作用较小相比，Gleason分级和Ki67 LI在前列腺癌中具有主要的预后意义。我们将syndecan-1鉴定为一种新的预后因素，并为CD-10表达的雄激素依赖性调节提供了证据。
