Levels of angiogenesis and expression of angiogenesis-related genes are prognostic for organ-specific metastasis of renal cell carcinoma
Levels of angiogenesis and expression of angiogenesis-related genes are prognostic for organ-specific metastasis of renal cell carcinoma
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DOI：
10.1002/cncr.20887
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发表时间：
2005-03-01
期刊：
影响因子：
6.2
通讯作者：
Shuin, T
中科院分区：
文献类型：
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作者：
Fukata, S;Inoue, K;Shuin, T
背景为了确定可用于预测肾透明细胞癌（CRCC）发展和转移位置的器官特异性转移相关因子，作者评估了原发性和转移性肿瘤中血管生成和血管生成相关基因的表达。他们通过免疫组织化学染色评估了肿瘤内微血管密度（VIVID），通过mRNA原位杂交评估了血管生成相关基因的表达，并确定了来自54名患者的92份原发性和转移性CRCC存档标本的临床病理学特征。所有38个科，高知医科大学，转移瘤标本切除24例。原发肿瘤标本的病理分期（P = 0.026）是转移的重要预测因子，MVD（P = 0.000025）和School，Kochi，日本的比率也是如此。基质金属蛋白酶（MMPs）与E-钙粘蛋白（M/E比值; P = 0.000041）。转移性CRCC患者的原发肿瘤组织中MVD、MMP-2表达及M/E比值均显著增高（P < 0.05）。与原发瘤相比，转移瘤的微血管密度（MVD）、碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子（VEGF）、白细胞介素-8（IL-8）、基质金属蛋白酶（MMP）的高表达及M/E比值（P < 0.05）也明显增高。多因素分析显示，原发灶MVD和M/E比值是影响转移的独立预后因素（分别为P = 0.049和P = 0.001）。此外，转移瘤标本中长转移灶和淋巴结转移灶的M/E比值是影响转移的独立预后因素（分别为P = 0.01823和P = 0.03950）。目前的研究表明，血管生成和M/E比值是肾细胞癌转移的特异性预测因子，尤其是肺或淋巴结转移。因此，MMPs和E-cadherin可能成为控制或预防肾癌转移的新的治疗策略的相关靶点。(C)2005年美国癌症协会。
BACKGROUND. To identify organ-specific, metastasis-related factors that can be used to predict the development and location of metastasis of clear cell renal cell carcinoma (CRCC), the authors assessed the angiogenesis and the expression of angiogenesis-related genes in primary and metastatic tumors.METHODS. They evaluated intratumoral microvessel density (VIVID) by immuno-histochemical staining, assessed the expression of angiogenesis- related genes by mRNA in situ hybridization, and determined the clinicopathologic characteristics of 92 archival specimens of primary and metastatic CRCCs from 54 patients. All 38 Department of Urology, Kochi Medical School, metastatic tumor specimens were resected from 24 patients.RESULTS. The pathologic stage (P = 0.026) of the primary tumor specimen was an important predictor for metastasis, as were MVD (P = 0.000025) and the ratio of School, Kochi, Japan. matrix metalloproteinases (MMPs) to E-cadherin (M/E ratio; P = 0.000041). In addition, primary turner specimens resected from patients with metastatic CRCCs had high MVD, high levels of MMP-2 expression, and a high M/E ratio (P < 0.05). Relative to the primary tumors, the metastatic tumors also had high MVD), overexpression of basic fibroblast growth factor, vascular endothelial growth factor, interleukin-8, MMPs, and a high M/E ratio (P < 0.05). Multivariate analysis revealed that MVD and the M/E ratio in the primary tumor were independent prognostic factors for metastasis (P = 0.049 and P = 0.001, respectively). Furthermore, the M/E ratio in metastatic turner specimens resected from the long and lymph node was an independent prognostic factor for metastasis (P = 0.01823 and P = 0.03950, respectively).CONCLUSIONS. The Current study indicated that angiogenesis and M/E ratio were specific predictors for metastases of RCC, especially to the lung Or lymph node. Therefore, MMPs and E-cadherin could be relevant targets for novel therapeutic strategies to control or prevent the metastasis of RCC. (C) 2005 American Cancer Society.