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The Prognostic Value of Angiogenesis Factor Expression for Predicting Recurrence and Metastasis of Bladder Cancer after Neoadjuvant Chemotherapy and Radical Cystectomy¹

Departments of Urology and Cancer Biology [K. I., J. W. S., P. S., C. P. N. D.] and Genitourinary Medical Oncology [R. M.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, and Department of Urology, Kochi Medical School, Kochi, Japan [K. I., T. K., C. Y., T. S.]

To determine the prognostic value of angiogenesis factor expression for patients with muscle-invasive transitional cell carcinoma (TCC) of the bladder treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) chemotherapy and radical cystectomy, we evaluated the expression of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8) by in situ hybridization, and we determined microvessel density (MVD) by immunohistochemistry. These factors were evaluated in 55 biopsy specimens prior to therapy and in the cystectomy specimens of 51 patients after completion of therapy. By univariate analysis, VEGF expression and MVD in the biopsy specimens were significant predictors of disease recurrence. By multivariate analysis, only VEGF expression was an independent prognostic factor. Pathological stage, bFGF expression, and MVD in the cystectomy specimens after therapy were all independent prognostic factors for disease recurrence. The results of this exploratory study indicate that the expression levels of VEGF and bFGF as indicated by in situ hybridization and MVD as indicated by immunohistochemistry identify patients with muscle-invasive TCC who are at high risk of developing metastasis after aggressive therapy with systemic M-VAC chemotherapy and radical cystectomy.

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