Li Rile, Younes Mamoun, Wheeler Thomas M, Scardino Peter, Ohori Makato, Frolov Anna, Ayala Gustavo
Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
Prostate. 2004 Feb 1;58(2):193-9. doi: 10.1002/pros.10321.
The growth and dissemination of tumors has been associated with angiogenesis, which is regulated by a group of polypeptide factors including vascular endothelial growth factor-C (VEGF-C). VEGF-C binds its receptor, vascular endothelial growth factor receptor-3 (VEGFR-3) to promote growth of tumor-associated lymphatic vessels.
In this study, microarray technology was used to build tissue arrays of normal prostate, benign prostate hyperplasia (BPH) and prostate carcinomas (PCa) using tissues from 640 patients. Slides were sectioned and stained with a polyclonal antibody to VEGFR-3 using a standard immunoperoxidase method and digitized. Immunoreactivity was scored using a 0-3+ semiquantitation scoring system for both intensity and percentage. The sum index was obtained by totaling the scores.
VEGFR-3 is expressed in normal prostate, BPH, and PCa, but VEGFR-3 expression is up-regulated in PCa. We also found that VEGFR-3 is correlated with pre-operative prostate-specific antigen (Pre-PSA), Gleason score, and lymph node metastasis. The recurrence-free 5-year survival in cases with lower sum index (0-3) was significantly higher than that in cases with higher sum index (4-6) (77.3, 69.6%, respectively, P = 0.037) by Kaplan-Meier actuarial model.
Our data suggest that VEGFR-3 expression is associated with tumor progression and may play an important role in facilitating lymphatic spread of PCa; high-level of VEGFR-3 expression in prostate cancer cells increases the risk of biochemical recurrence in prostate cancer patients treated by radical prostatectomy.
肿瘤的生长和扩散与血管生成有关，血管生成受包括血管内皮生长因子-C（VEGF-C）在内的一组多肽因子调节。VEGF-C与其受体血管内皮生长因子受体-3（VEGFR-3）结合，促进肿瘤相关淋巴管的生长。
在本研究中，利用微阵列技术，使用640例患者的组织构建正常前列腺、良性前列腺增生（BPH）和前列腺癌（PCa）的组织阵列。将玻片切片，采用标准免疫过氧化物酶法用抗VEGFR-3多克隆抗体染色并数字化。使用0-3+半定量评分系统对强度和百分比进行免疫反应性评分。通过将分数相加获得总和指数。
VEGFR-3在正常前列腺、BPH和PCa中均有表达，但在PCa中VEGFR-3表达上调。我们还发现VEGFR-3与术前前列腺特异性抗原（Pre-PSA）、Gleason评分和淋巴结转移相关。根据Kaplan-Meier精算模型，总和指数较低（0-3）的病例5年无复发生存率显著高于总和指数较高（4-6）的病例（分别为77.3%、69.6%，P = 0.037）。
我们的数据表明，VEGFR-3表达与肿瘤进展相关，可能在促进PCa的淋巴扩散中起重要作用；前列腺癌细胞中高水平的VEGFR-3表达增加了接受根治性前列腺切除术的前列腺癌患者生化复发的风险。
