Eppenberger U, Kueng W, Schlaeppi J M, Roesel J L, Benz C, Mueller H, Matter A, Zuber M, Luescher K, Litschgi M, Schmitt M, Foekens J A, Eppenberger-Castori S
Stiftung Tumorbank Basel, Department of Research, University Clinics/Kantonsspital Basel, Switzerland.
J Clin Oncol. 1998 Sep;16(9):3129-36. doi: 10.1200/JCO.1998.16.9.3129.
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.
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.
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 < or = 20% likelihood of recurrence within 7 years.
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.
比较肿瘤血管生成因子（血管内皮生长因子[VEGF]、血管生成素和碱性成纤维细胞生长因子[bFGF]）、肿瘤蛋白水解因子（尿激酶型纤溶酶原激活剂[uPA]和纤溶酶原激活剂抑制剂-1[PAI-1]）以及传统肿瘤标志物（分期、分级和类固醇受体）对早期乳腺癌预后的影响。
在原发性临床研究中，对305例原发性乳腺肿瘤的冷冻活检标本进行肿瘤血管生成及其他因子检测。采用化学发光免疫吸附测定法（ICMA）评估VEGF表达；采用酶联免疫吸附测定法（ELISA）检测血管生成素、bFGF、uPA和PAI-1；采用酶免疫测定法（EIA）检测类固醇受体（雌激素受体[ER]和孕激素受体[PgR]）。在验证性临床研究中，在另一家机构收集了另一组190例淋巴结阴性的原发性乳腺肿瘤样本。
原发性研究的单因素分析显示，VEGF水平与复发呈正相关（P<.001）。血管生成素水平与总体人群的疾病复发呈正相关（P<.005），但在淋巴结阴性亚组中无相关性。未发现肿瘤bFGF水平与患者生存率之间存在显著相关性。多因素回归分析显示，无复发生存期（RFS）的唯一独立预测因素是VEGF、uPA和淋巴结状态。在验证集中，VEGF和uPA值的分布与原发性研究相似；VEGF和uPA均低表达的患者在7年内复发可能性≤20%。
独立的原发性和验证性临床研究均表明，肿瘤VEGF水平是肿瘤血管生成和蛋白水解的几种标志物中最重要的预后参数。
