[HTML][HTML] Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma

N Weidner, JP Semple, WR Welch… - New England Journal …, 1991 - Mass Medical Soc
N Weidner, JP Semple, WR Welch, J Folkman
New England Journal of Medicine, 1991Mass Medical Soc
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 immunocyto …
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 immunocyto-chemically for factor VIII. The microvessels were carefully counted (per 200×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≤0.001, respectively). For each 10-microvessel increase in the count per 200× 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× 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× 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. (N Engl J Med 1991;324:1–8.)
The New England Journal Of Medicine