Proliferation of Immature Tumor Vessels Is a Novel Marker of Clinical Progression in Prostate Cancer
Proliferation of Immature Tumor Vessels Is a Novel Marker of Clinical Progression in Prostate Cancer
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DOI：
10.1158/0008-5472.can-08-4417
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发表时间：
2009-06-01
期刊：
影响因子：
11.2
通讯作者：
Akslen, Lars A.
中科院分区：
文献类型：
--
作者：
Gravdal, Karsten;Halvorsen, Ole J.;Akslen, Lars A.
Nestin（神经上皮干细胞蛋白）在未成熟的内皮细胞中表达，我们在这里介绍Nestin和Ki-67作为一种新的血管生成标记物在组织切片上的共表达。包括血管内皮生长因子（VEGF）-A和缺氧诱导因子-1 α（HIF-1 α）的表达，我们研究了前列腺癌与疾病进展的关系。纳入了不同的患者系列。对104例长期随访的根治性前列腺切除术、33例去势抵抗性前列腺癌、28例非骨转移瘤、13例骨转移瘤和41例良性前列腺增生的切片进行Nestin/Ki-67、VEGF-A和HIF-1 α免疫染色。巢蛋白/Ki-67阳性血管的血管增殖在“热点”区域内计数。去势抵抗性前列腺癌和转移瘤的中位血管增殖计数是局限性前列腺癌和前列腺增生的4- 5倍（P < 0.0005）。在局限性癌症中，高血管增生与不良临床病理特征显著相关，并且在多变量分析中是生化失败（P < 0.005）、临床复发（P = 0.005）和骨转移（P = 0.025）的强有力的独立预测因子。去势抵抗性癌症的特征是VEGF-A表达减少和HIF-1 α表达增加，血管增殖与该组患者生存率降低相关。因此，血管增生是独立的前列腺癌预后的重要性。与局限性癌相比，去势抵抗病例和转移性病灶的血管增生显著增加。去势抵抗性肿瘤表现出弱VEGF-A但强HIF-1 α表达。这些新的数据可能对前列腺癌患者的临床评估和治疗产生影响。[Cancer lies 2009;69（11）：4708-15]
Nestin (neuroepithelial stem cell protein) is expressed in immature endothelial cells, and we here introduce coexpression of Nestin and Ki-67 as a novel angiogenesis marker on tissue sections. Including vascular endothelial growth factor (VEGF)-A and hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression, we studied relation to disease progression in prostate cancer. Different patient series were included. Sections from 104 radical prostatectomies with long follow-up, 33 castration-resistant prostate cancers, 28 nonskeletal metastases, 13 skeletal metastases, and 41 benign prostatic hyperplasias were immunostained for Nestin/Ki-67, VEGF-A, and HIF-1 alpha. Vascular proliferation by Nestin/Ki-67-positive vessels was counted within "hotspot" areas. Median vascular proliferation counts were 4- to 5-fold higher in castration-resistant prostate cancers and metastases versus localized cancers and prostatic hyperplasias (P < 0.0005). Among localized cancers, high vascular proliferation was significantly related to adverse clinicopathologic features and was a strong and independent predictor of biochemical failure (P < 0.005), clinical recurrence (P = 0.005), and skeletal metastasis (P = 0.025) in multivariate analysis. Castration-resistant cancers were characterized by reduced VEGF-A and increased HIF-1 alpha expression, and vascular proliferation was associated with reduced patient survival in this group. Thus, vascular proliferation was of independent prognostic importance among prostate cancers. When compared with localized cancers, vascular proliferation was significantly increased in castration-resistant cases and metastatic lesions. The castration-resistant tumors exhibited weak VEGF-A but strong HIF-1 alpha expression. These novel data might have an effect on clinical evaluation and treatment of prostate cancer patients. [Cancer lies 2009;69(11):4708-15]