© 1997 by Oxford University Press
Journal Of The National Cancer Institute, Vol 89, 139-147, Copyright © 1997 by Oxford University Press
G Gasparini, M Toi, M Gion, P Verderio, R Dittadi, M Hanatani, I Matsubara, O Vinante, E Bonoldi, P Boracchi, C Gatti, H Suzuki and T Tominaga
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 < .001). In the multivariate
analysis, the first-order interaction term of VEGF and estrogen receptor
was also prognostic for overall survival (likelihood ratio test; P = .05).
CONCLUSIONS: The results show that cytosolic levels of VEGF in tumor tissue
samples are indicative of prognosis for patients with node- negative breast
carcinoma.
ARTICLES
Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma
Department of Oncology, St. Bortolo Regional Medical Centre, Vicenza, Italy.
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