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Molecular Oncology, Markers, Clinical Correlates |
Cattedra di Oncologia Medica, Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica [S. D. P., C. C., F. C., M. D. L., S. P., A. R., G. T., A. R. B.]; Istituto di Anatomia Patologica [L. P., A. D., G. Pett.] and Cattedra di Oncologia Chirurgica [G. Petr.]; Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli "Federico II," 80131 Naples, Italy
We measured neovascularization, epidermal growth factor receptor, and c-erbB-2 expression in a consecutive series of 233 surgically resected axillary lymph node-negative breast cancer patients with a long-term follow-up to define the usefulness of these parameters as independent prognostic indicators of overall survival (OAS). Microvessel count (MVC), as a measure of neovascularization, was determined using a monoclonal antibody against human factor VIII-related antigen. The median MVC of 20 (range, 476) was used as a cutoff value for discriminating between low and high vascularized tumors. Epidermal growth factor receptor and c-erbB-2 expression were evaluated by immunohistochemistry. Tumors were considered positive if >10% of the cells showed specific membrane staining. OAS curves were estimated by the Kaplan-Meier method. The indepen-dent prognostic effect of each variable was determined with the Cox proportional hazards model. High MVC (P = 0.04), high nuclear grade (P = 0.005), and high S-phase (P = 0.02) significantly affected OAS at univariate analysis. In a Cox multivariate analysis, the characteristics with an independent prognostic effect on OAS were: MVC (relative hazard, 2.12; 95% confidence interval, 1.183.81; P = 0.01) and nuclear grade (relative hazard, 2.83; 95% confidence interval, 1.127.17; P = 0.01). These results demonstrate that quantification of neovascularization adds useful independent prognostic information on survival in node-negative breast cancer patients with long-term follow-up.
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