TUMOR ANGIOGENESIS AND METASTASIS - CORRELATION IN INVASIVE BREAST-CARCINOMA
TUMOR ANGIOGENESIS AND METASTASIS - CORRELATION IN INVASIVE BREAST-CARCINOMA
复制标题
DOI：
10.1056/nejm199101033240101
复制
发表时间：
1991-01-03
影响因子：
158.5
通讯作者：
FOLKMAN, J
中科院分区：
文献类型：
--
作者：
WEIDNER, N;SEMPLE, JP;FOLKMAN, J
背景资料。实验证据表明，肿瘤超过一定大小的生长需要血管生成，这也可能允许转移。为探讨肿瘤血管生成与乳腺癌转移的关系，我们对49例初发浸润性癌(30例有转移者，19例无转移者)的微血管(毛细血管和小静脉)进行计数和分级。利用光学显微镜，我们通过对血管内皮细胞进行第八因子免疫细胞化学染色来突出血管。在不知道患者预后、有无转移或任何其他相关变量的情况下，对微血管进行仔细计数(每200个视野)，并在新生血管最活跃的区域对其密度进行分级(1-4+)。微血管计数和密度分级与转移性疾病相关。转移组平均(+/-SD)计数为101+/-49.3支，分级为2.95+/-1.00支。无转移组相应的P值分别为-45+/-21.1和1.38+/-0.82(P分别为0.003和P<0.001)。每200x视野内微血管计数每增加10个微血管，转移风险增加1.59倍(95%可信区间为1.19至2.12；P=0.003)。微血管计数和密度分级也与远处转移有关。每200x视野内微血管计数每增加10个微血管，远处转移的风险增加1.17倍(95%可信区间为1.02至1.34；P=0.029)。浸润性乳腺癌中新生血管最密集的区域中每200x视野内微血管的数量可能是腋窝淋巴结或远处(或两者兼而有之)转移疾病的独立预测指标。因此，肿瘤血管生成的评估可能被证明对选择早期乳腺癌患者进行侵袭性治疗很有价值。
Background. Experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit metastasis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, we counted microvessels (capillaries and venules) and graded the density of microvessels within the initial invasive carcinomas of 49 patients (30 with metastases and 19 without).Methods. Using light microscopy, we highlighted the vessels by staining their endothelial cells immunocytochemically for factor VIII. The microvessels were carefully counted (per 200 x field), and their density was graded (1 to 4+), in the most active areas of neovascularization, without knowledge of the outcome in the patient, the presence or absence of metastases, or any other pertinent variable.Results. Both microvessel counts and density grades correlated with metastatic disease. The mean (+/- SD) count and grade in the patients with metastases were 101 +/- 49.3 and 2.95 +/- 1.00 vessels, respectively. The corresponding values in the patients without metastases were significantly lower - 45 +/- 21.1 and 1.38 +/- 0.82 (P = 0.003 and P less-than-or-equal-to 0.001, respectively). For each 10-microvessel increase in the count per 200 x field, there was a 1.59-fold increase in the risk of metastasis (95 percent confidence interval, 1.19 to 2.12; P = 0.003). The microvessel count and density grade also correlated with distant metastases. For each 10-microvessel increase in the vessel count per 200 x field, there was a 1.17-fold increase in the risk of distant metastasis (95 percent confidence interval, 1.02 to 1.34; P = 0.029).Conclusions. The number of microvessels per 200 x field in the areas of most intensive neovascularization in an invasive breast carcinoma may be an independent predictor of metastatic disease either in axillary lymph nodes or at distant sites (or both). Assessment of tumor angiogenesis may therefore prove valuable in selecting patients with early breast carcinoma for aggressive therapy.