© 1992 by Oxford University Press
Journal of the National Cancer Institute, Vol. 84, No. 24, 1875-1887,
December 16, 1992
© 1992 Oxford University Press
Tumor Angiogenesis: A New Significant and Independent Prognostic Indicator in Early-Stage Breast Carcinoma
Department of Pathology, University of California San Francisco
Departments of Surgery and Anatomy and Cellular Biology, Children's Hospital, Harvard Medical School Boston, Mass
St. Bortolo Regional Medical Center Vicenza-Veneto, Italy
Statistical and Data Base Consulting Gardener House, Boston, Mass
Lawrence Livermore National Laboratory, University of California Livermore
*Correspondence to: Noel Weidner, M.D., Department of Pathology, University of California, San Francisco, Box 0102, San Francisco, CA 94143-0102.
Address reprint requests to: Giampietro Gasparini, M.D., Department of Oncology and Radiotherapy, St. Bortolo Regional Hospital, 36100 Vicenza, Italy.
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 micros copy, 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
.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 200 x field experienced tumor recurrence within 33 months of diagnosis, compared with less than 5% of the patients with breast carcinoma having 33 or fewer microvessels per 200x field. Moreover, microvessel density was the only statistically significant predictor of overall survival among node-negative women (P<.001). Only microvessel density (P<.001) and histologic grade (P=.04) showed statistically significant correlations with relapse-free survival in the node-negative subset. Conclusions: Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is an independent and highly significant prognostic indicator for overall and relapse-free survival in patients with early-stage breast carcinoma (I or II by International Union Against Cancer criteria). Implications: Such an indicator would be useful in selection of those node-negative patients with breast carcinoma who are high risk for having occult metastasis at presentation. These patients could then be given systemic adjuvent therapy. [J Natl Cancer Inst 84:1875–1887, 1992]
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