Markers of tumor angiogenesis and proteolysis independently define high- and low-risk subsets of node-negative breast cancer patients
Markers of tumor angiogenesis and proteolysis independently define high- and low-risk subsets of node-negative breast cancer patients
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DOI：
10.1200/jco.1998.16.9.3129
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发表时间：
1998-09-01
影响因子：
45.3
通讯作者：
Eppenberger-Castori, S
中科院分区：
文献类型：
--
作者：
Eppenberger, U;Kueng, W;Eppenberger-Castori, S
目的：比较肿瘤血管生成因子(血管内皮生长因子、血管生成素和碱性成纤维细胞生长因子)、肿瘤蛋白分解因子(尿激酶型纤溶酶原激活物[uPA]和纤溶酶原激活物抑制物-1[PAI-1])和常规肿瘤标志物(分期、分级和类固醇受体)对早期乳腺癌预后的影响。采用化学发光免疫吸附分析法(ICMA)检测血管内皮生长因子的表达，用酶联免疫吸附分析法检测血管生成素、碱性成纤维细胞生长因子、uPA和PAI-1的表达，用酶免疫分析法检测类固醇激素受体(雌激素受体[ER]和孕激素受体[PGR])的表达。在验证性临床研究中，另一组190个结节阴性的原发乳腺肿瘤样本在单独的机构收集。结果：初步研究的单因素分析显示，VEGF水平与复发呈正相关(P<；.001)。在整个集体组中，血管生成素水平与疾病复发呈正相关(P<；0.005)，但在结节阴性子集内则不相关。未发现肿瘤碱性成纤维细胞生长因子水平与患者生存期之间的显著相关性。在多变量回归分析中，唯一独立预测无复发生存率(RFS)的因素是血管内皮生长因子、uPA和淋巴结状况。在验证集中，VEGF和uPA的值分布与原始研究中的相似；低表达的VEGF和uPA可以确定患者在7年内复发的可能性小于或等于20%。结论：单独的初级和验证性临床研究一致认为，在肿瘤血管生成和蛋白分解的几个标志物中，肿瘤血管内皮生长因子水平是最重要的预后参数。I Clin Oncol16：3129-3136。(C)1998年由美国临床肿瘤学会主办。
Purpose: To compare the prognostic impact of tumor angiogenesis factors (vascular endothelial growth factor [VEGF], angiogenin, and basic fibroblast growth factor [bFGF]), tumor proteolysis factors (urokinase-type plasminogen activator [uPA] and plasminogen activator inhibitor-1 [PAI-1]), and conventional tumor markers (stage, grade, and steroid receptors) in early breast cancer.Patients and Methods: In the primary clinical study, tumor angiogenesis and other factors were detected in frozen biopsies from 305 primary breast tumors. VEGF expression was assessed by chemiluminescence immunosorbent assay (ICMA); angiogenin, bFGF, uPA, and PAI-1 by enzyme-linked immunosorbent assay (ELISA); and steroid receptors (estrogen receptor [ER] and progesterone receptor [PgR]) by enzyme immunoassay (EIA). In the validating clinical study another set of 190 node-negative primary breast tumor samples were collected at a separate institution.Results: Univariate analysis of the primary study showed that VEGF levels were positively correlated with recurrence (P < .001). Angiogenin levels were positively correlated with disease relapse (P < .005) for the overall collective group, but not within the node-negative subset. No significant correlations were found between tumor bFGF levels and patient survival. In multivariate regression analysis, the only independent predictors of relapse-free survival (RFS) were VEGF, uPA, and lymph node status. In the validation set, the distribution of VEGF and uPA values were similar to those in the primary study; low expression of both VEGF and uPA identified patients with a less than or equal to 20% likelihood of recurrence within 7 years.Conclusion: Separate primary and validating clinical studies concur that tumor VEGF level is the most important prognostic parameter among several markers of tumor angiogenesis and proteolysis. I Clin Oncol 16:3129-3136. (C) 1998 by American Society of Clinical Oncology.