Over expression of insulin-like growth factor binding protein 3 in clear cell renal cell carcinoma.

ABSTRACT

PURPOSE: We recently reported that IGFBP-3 (insulin-like growth factor binding protein 3) is one of the top genes that are over expressed in clear cell renal cell carcinoma. We further investigated IGFBP-3 expression in renal tumors using gene expression microarrays, immunohistochemistry and Western blotting. MATERIALS AND METHODS: A total of 70 renal neoplasms were subjected to gene expression microarrays using gene chips containing 21,632 cDNA clones. IGFBP-3 expression was measured in each renal epithelial neoplasm. In addition, we performed immunohistochemistry for IGFBP-3 in 127 renal epithelial tumors, including 58 clear cell renal cell carcinomas. Moreover, IGFBP-3 staining intensity was evaluated to determine whether there was a correlation with Fuhrman grade. Lastly, Western blot was performed to confirm IGFBP-3 levels. RESULTS: On microarray analysis of 70 renal neoplasms IGFBP-3 mRNA was increased in 63% of clear cell renal cell carcinomas (27 of 43) but in only 4% of other renal tumors (1 of 24). On immunohistochemistry 74% of clear cell renal cell carcinomas (43 of 58) showed IGFBP-3 immunoreactivity compared to only 9% of other renal neoplasms (6 of 69). High grade (Fuhrman grades 3 and 4) clear cell renal cell carcinomas showed higher IGFBP-3 staining intensity than low grade ones (15 of 17 vs 8 of 41). Western blot confirmed immunohistochemistry findings with the detection of high IGFBP-3 in clear cell renal cell carcinoma but not in other types of kidney tumors. CONCLUSIONS: With a combination of cDNA microarrays, Western blot and immunohistochemistry we confirmed that IGFBP-3 is a marker for clear cell renal cell carcinoma. Furthermore, higher IGFBP-3 expression was associated with higher Fuhrman grade.