Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma
Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma
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DOI：
10.1093/jnci/89.2.139
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发表时间：
1997-01-15
期刊：
影响因子：
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通讯作者：
Tominaga, T
中科院分区：
文献类型：
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作者：
Gasparini, G;Toi, M;Tominaga, T
背景：对于接受手术或手术加放疗的淋巴结阴性乳腺癌患者（即淋巴结未检测到转移的患者），临床结果通常是阳性的。然而，在大约30%的患者中，这种疾病会复发，并有死亡的危险。确定有效的新预后指标将提高识别复发高风险患者的能力。乳腺癌可能需要肿瘤组织内大量新血管的发展，并且已知实体瘤的生长和转移依赖于这种血管生成。肿瘤细胞向血管生成表型的转化可能发生在血管生成生长因子和血管生成抑制剂平衡的改变之前。目的：本研究旨在确定在淋巴结阴性乳腺癌女性原发肿瘤中测量的血管内皮生长因子（VEGF）蛋白水平是否与已知的预后因素和患者生存相关。VEGF是一种有效的内皮生长因子，也是血管通透性和血管生成的介质。方法：使用选择性酶免疫分析法，测定260例淋巴结阴性乳腺癌患者手术获得的原发肿瘤组织的细胞质提取物中VEGF蛋白的水平，这些患者接受过手术治疗，有或没有放射治疗，但没有辅助治疗，随访时间中位数为66个月。分别使用Kolmogorov-Smirnov检验和单因素及多因素Cox分析来检验VEGF浓度与其他预后二分类变量或临床结果之间的关系。VEGF与激素受体（即雌激素和孕激素受体）之间的关系通过Spearman相关分析进行检验。所有P值均采用双侧统计检验。结果：260例患者中有247例（95%）的肿瘤可检测到VEGF，浓度范围为5.0至6523 pg/mg蛋白（中位数为126.25 pg/mg蛋白）。VEGF与其他预后因素（如年龄、绝经状态、组织学肿瘤类型、肿瘤大小和激素受体）之间没有统计学意义的关联。在单因素和多因素分析（似然比检验；所有四个P值）中发现VEGF水平对无复发和总生存均有预后作用
Background: The clinical outcome is generally positive for patients with node-negative breast carcinoma (i.e., those who do not have detectable metastases in the lymph nodes) who have been treated with surgery or surgery plus radiation therapy. In about 30% of the patients, however, the disease recurs, and they are at risk of death. Determination of valid new prognostic indicators would improve the ability to identify patients at high risk of recurrence. Breast cancer can entail substantial development of new blood vessels within the tumor tissue, and it is known that the growth and metastasis of solid tumors are dependent on such angiogenesis. The conversion of tumor cells to an angiogenic phenotype may be preceded by a change in the balance of angiogenic growth factors and angiogenesis inhibitors. Purpose: This study was conducted to determine if the levels of vascular endothelial growth factor (VEGF) protein, a potent endothelial growth factor and mediator of vascular permeability and angiogenesis, measured in the primary tumors of women with node-negative breast cancer are associated with known prognostic factors and patient survival. Methods: By use of a selective enzymatic immunoassay, levels of VEGF protein were measured in cytosolic extracts of primary tumor tissue surgically obtained from 260 women with node-negative breast carcinoma who had been treated with surgery with or without radiation therapy but not with adjuvant therapy and who had been followed for a median time of 66 months. The relationships between VEGF concentrations and other prognostic dichotomous variables or clinical outcome were tested by the use of the Kolmogorov-Smirnov test and univariate and multivariate Cox analyses, respectively. The relationship between VEGF and hormone receptors (i.e., those for estrogen and progesterone) was examined by the use of Spearman's correlation analyses. All P values resulted from the use of two-sided statistical tests. Results: Tumors from 247 (95%) of the 260 patients had detectable VEGF, ranging in concentration from 5.0 to 6523 pg/mg protein (median, 126.25 pg/mg protein). No statistically significant associations were found between VEGF and the other prognostic factors (e.g., age, menopausal status, histologic tumor type, tumor size, and hormone receptors) examined. Levels of VEGF were found to be prognostic for both relapse-free and overall survival in univariate and multivariate analyses (likelihood ratio tests; all four P values