Expression levels of genes that regulate metastasis and angiogenesis correlate with advanced pathological stage of renal cell carcinoma

We examined the expression levels of a number of metastasis-related genes t o determine the relationship of these levels to the development of metastas is in renal cell carcinoma. Gene expression was examined in 46 formalin-fix ed, paraffin-embedded, archival specimens of primary organ-confined, clear- cell, renal cell carcinoma from patients who had undergone radical nephrect omy, Twenty samples were from patients who did not have metastasis after a median of 48 months; 26 were from patients with either synchronous or metac hronous metastases, Microvessel density was assessed by anti-CD-34 immunohi stochemical analysis. The expression levels of basic fibroblast growth fact or (bFGF), vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), matrix metalloproteinases (MMP)-2 and -9, and E-cadherin were examined at the periphery of the tumor by a colorimetric in situ mRNA. The expression l evels of bFGF, VEGF, IL-8, MMP-2, and MMP-9 were significantly higher in pr imary renal tumors from patients with either synchronous or metachronous me tastases than those who were disease-free at a median of 48 months of follo w-up, Multivariate analysis of disease-free survival showed that the ratio of MMP-9 to E-cadherin (P = 0.012) and the expression level of bFGF express ion (P = 0.045), were independent predictors for the development of metasta ses, The expression levels of bFGF, VEGF, and IL-8 did not correlate with m icrovessel density, which in itself was not a significant predictor of prog ression (P = 0.21). In summary, expression levels of genes that regulate me tastasis angiogenesis can predict the metastatic potential in individual pa tients with organ-confined clear-cell renal carcinoma.