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The Prognostic Value of Angiogenesis and Metastasis-related Genes for Progression of Transitional Cell Carcinoma of the Renal Pelvis and Ureter

Department of Urology, Kochi Medical School, Nankoku, Kochi, 783-8505 Japan [K. I., M. K., S. F., C. Y., T. S.], and Departments of Cancer Biology [J. W. S., C. P. N. D.] and Pathology [P. T.], The University of Texas M. D. Cancer Center, Houston, Texas 77030

Purpose: We reported previously that angiogenesis evaluated by intratumor microvessel density (MVD), expression of such angiogenic factors as vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (bFGF), and the matrix metalloproteinase-9:E-cadherin ratio (M:E ratio) could identify patients with advanced transitional cell carcinoma (TCC) of the bladder for whom chemotherapy and cystectomy will be unsuccessful. In the present study, we evaluated the significance of the M:E ratio as a predictor for prognosis for patients with TCC in the upper urinary tract (TCC-UUT).

Experimental Design: We evaluated MVD by immunohistochemistry and the expression of angiogenic and metastasis-related factors by in situ hybridization in 55 nephroureterectomy specimens from patients who received no neoadjuvant therapy. The expression of angiogenesis, angiogenic and metastasis-related factors, and clinicopathological characteristics were evaluated for their correlation with metastasis, recurrence, and disease prognosis.

Results: We found that tumor grade and pathological stage were important predictors for metastasis and survival in these patients. The expression level of matrix metalloproteinase type 9 (MMP-9) and type 2 (MMP-2) and the M:E ratio correlated with MVD. Increased MVD, elevated expression levels of MMP-9 and MMP-2, and a higher M:E ratio were associated with poor prognosis. Moreover, lower expression levels of E-cadherin were associated with fewer recurrences in the urinary bladder. Multivariate analysis indicated that the M:E ratio and E-cadherin expression were independent prognostic factors for disease progression and intravesical recurrence, respectively.

Conclusion: We suggest that the M:E ratio and E-cadherin expression may be targets for novel therapeutic strategies.

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