血管生成水平及血管生成相关基因的表达对肾细胞癌器官特异性转移具有预后价值。

Levels of angiogenesis and expression of angiogenesis-related genes are prognostic for organ-specific metastasis of renal cell carcinoma.

作者信息

Fukata Satoshi, Inoue Keiji, Kamada Masayuki, Kawada Chiaki, Furihata Mutsuo, Ohtsuki Yuji, Shuin Taro

机构信息

Department of Urology, Kochi Medical School, Kochi, Japan.

出版信息

Cancer. 2005 Mar 1;103(5):931-42. doi: 10.1002/cncr.20887.

DOI:10.1002/cncr.20887

PMID:15685621

Abstract

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 (MVD) by immunohistochemical 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 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 matrix metalloproteinases (MMPs) to E-cadherin (M/E ratio; P=0.000041). In addition, primary tumor 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 tumor specimens resected from the lung 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.

摘要

背景

为了确定可用于预测透明细胞肾细胞癌（CRCC）转移发生及部位的器官特异性转移相关因子，作者评估了原发性肿瘤和转移性肿瘤中的血管生成及血管生成相关基因的表达情况。

方法

他们通过免疫组化染色评估肿瘤内微血管密度（MVD），通过mRNA原位杂交评估血管生成相关基因的表达，并确定了54例患者的92份原发性和转移性CRCC存档标本的临床病理特征。所有38份转移性肿瘤标本均取自24例患者。

结果

原发性肿瘤标本的病理分期（P = 0.026）是转移的重要预测指标，MVD（P = 0.000025）以及基质金属蛋白酶（MMPs）与E-钙黏蛋白的比值（M/E比值；P = 0.000041）也是如此。此外，从发生转移性CRCC的患者身上切除的原发性肿瘤标本具有较高的MVD、较高水平的MMP-2表达以及较高的M/E比值（P < 0.05）。相对于原发性肿瘤，转移性肿瘤同样具有较高的MVD、碱性成纤维细胞生长因子、血管内皮生长因子、白细胞介素-8、MMPs的过表达以及较高的M/E比值（P < 0.05）。多因素分析显示，原发性肿瘤中的MVD和M/E比值是转移的独立预后因素（分别为P = 0.049和P = 0.001）。此外，从肺和淋巴结切除的转移性肿瘤标本中的M/E比值是转移的独立预后因素（分别为P = 0.01823和P = 0.03950）。