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


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.
Chuang
Shang-Tian
ST
Department of Pathology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Patton
Kurt T
KT
Schafernak
Kristian T
KT
Papavero
Veronica
V
Lin
Fan
F
Baxter
Robert C
RC
Teh
Bin Tean
BT
Yang
Ximing J
XJ
D015415:Biomarkers / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology*; D046228:Microarray Analysis; D012333:RNA, Messenger / Q000378:metabolism
D015415:Biomarkers; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger