TUMOR ANGIOGENESIS - A NEW SIGNIFICANT AND INDEPENDENT PROGNOSTIC INDICATOR IN EARLY-STAGE BREAST-CARCINOMA
TUMOR ANGIOGENESIS - A NEW SIGNIFICANT AND INDEPENDENT PROGNOSTIC INDICATOR IN EARLY-STAGE BREAST-CARCINOMA
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DOI：
10.1093/jnci/84.24.1875
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发表时间：
1992-12-16
影响因子：
10.3
通讯作者：
GASPARINI, G
中科院分区：
文献类型：
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作者：
WEIDNER, N;FOLKMAN, J;GASPARINI, G
背景：腋窝淋巴结状况一直是可手术乳腺癌最重要的预后因素，但它并不能完全解释不同的疾病结局。更准确的预后指标将有助于选择疾病复发和死亡的高风险患者作为系统辅助治疗的候选对象。我们最近的发现表明，浸润性乳腺癌中的微血管密度(计数或分级)(肿瘤血管生成的一个指标)与转移有关，因此可能是一个预后指标。目的：本研究旨在进一步明确微血管密度与乳腺癌总生存率和无复发生存率的关系，以及与其他已报道的预后指标的关系。方法：在一项对165名连续患者进行的前瞻性、盲法研究中，采用免疫细胞化学方法突出显示原发性浸润性乳腺癌内的微血管，以检测第VIII因子相关抗原。使用光学显微镜，我们在新生血管最活跃的区域每200X视野计数微血管，并分级微血管密度。通过单变量和多变量分析，这些发现与总体和无复发生存率、腋窝淋巴结状况和其他预后指标(中位随访51个月)相关。结果：在所有患者中，微血管密度与总存活率和无复发存活率有高度显著的相关性(P<或等于.001)，包括结节阴性和结节阳性亚组。每200X视野微血管超过100个的乳腺癌患者在确诊后33个月内肿瘤复发，相比之下，每200X视野微血管少于33个的乳腺癌患者中，只有不到5%的患者出现肿瘤复发。此外，微血管密度是预测淋巴结阴性妇女总生存率的唯一有统计学意义的指标(P
Background: Axillary lymph node status has been the most important prognostic factor in operable breast carcinoma, but it does not fully account for the varied disease outcome. More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are candidates for systemic adjuvant therapy. Our recent findings indicated that microvessel density (count or grade) in invasive breast carcinoma (a measure of tumor angiogenesis) is associated with metastasis and thus may be a prognostic indicator. Purpose: This study was designed to further define the relationship of microvessel density with overall and relapse-free survival and with other reported prognostic indicators in breast carcinoma. Methods: In a prospective, blinded study of 165 consecutive patients, the microvessels within primary invasive breast carcinoma were highlighted by immunocytochemical staining to detect factor VIII-related antigen. Using light microscopy, we counted microvessels per 200X field in the most active areas of neovascularization and graded microvessel density. These findings were correlated, by univariate and multivariate analyses, with overall and relapse-free survival, axillary node status, and other prognostic indicators (median follow-up, 51 months). Results: There was a highly significant (P less-than-or-equal-to .001) association of microvessel density with overall survival and relapse-free survival in all patients, including node-negative and node-positive subsets. All patients with breast carcinomas having more than 100 microvessels per 200X field experienced tumor recurrence within 33 months of diagnosis, compared with less than 5% of the patients with breast carcinoma having 33 or fewer micro-vessels per 200X field. Moreover, microvessel density was the only statistically significant predictor of overall survival among node-negative women (P