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

被引:35
作者
Chuang, Shang-Tian [2 ]
Patton, Kurt T. [2 ]
Schafernak, Kristian T. [2 ]
Papavero, Veronica [2 ]
Lin, Fan [3 ]
Baxter, Robert C. [4 ]
Teh, Bin Tean [5 ]
Yang, Ximing J. [1 ,2 ]
机构
[1] Cornell Univ, Weill Med Coll, Dept Pathol & Lab Med, New York, NY 10021 USA
[2] Northwestern Univ, Feinberg Sch Med, Northwestern Mem Hosp, Dept Pathol, Chicago, IL 60611 USA
[3] Geisinger Hlth Syst, Dept Pathol & Lab Med, Danville, PA USA
[4] Univ Sydney, Royal N Shore Hosp, Kolling Inst Med Res, St Leonards, NSW 2065, Australia
[5] Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI USA
关键词
kidney; carcinoma; renal cell; insulin-like growth factor binding protein 3; microarray analysis; tumor markers; biological;
D O I
10.1016/j.juro.2007.09.106
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:445 / 449
页数:5
相关论文
共 18 条
[11]   C-kit expression in renal oncocytomas and chromophobe renal cell carcinomas [J].
Huo, L ;
Sugimura, J ;
Tretiakova, MS ;
Patton, KT ;
Gupta, R ;
Popov, B ;
Laskin, WB ;
Yeldandi, A ;
Teh, BT ;
Yang, XMJ .
HUMAN PATHOLOGY, 2005, 36 (03) :262-268
[12]   Editorial: Insulin-like growth factor (IGF)-binding proteins in serum - Do they have additional roles besides modulating the endocrine IGF actions? [J].
Mohan, S ;
Baylink, DJ .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1996, 81 (11) :3817-3820
[13]   Treatment outcome and survival associated with metastatic renal cell carcinoma of non-clear-cell histology [J].
Motzer, RJ ;
Bacik, J ;
Mariani, T ;
Russo, P ;
Mazumdar, M ;
Reuter, V .
JOURNAL OF CLINICAL ONCOLOGY, 2002, 20 (09) :2376-2381
[14]   Circulating insulin-like growth factor-I and binding protein-3 and risk of prostate cancer [J].
Severi, Gianluca ;
Morris, Howard A. ;
MacInnis, Robert J. ;
English, Dallas R. ;
Tilley, Wayne D. ;
Hopper, John L. ;
Boyle, Peter ;
Giles, Graham G. .
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2006, 15 (06) :1137-1141
[15]  
Takahash M, 2005, INT J ONCOL, V26, P923
[16]   Gene expression profiling of clear cell renal cell carcinoma: Gene identification and prognostic classification [J].
Takahashi, M ;
Rhodes, DR ;
Furge, KA ;
Kanayamat, H ;
Kagawa, S ;
Haab, BB ;
Teh, BT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (17) :9754-9759
[17]   Molecular subclassification of kidney tumors and the discovery of new diagnostic markers [J].
Takahashi, M ;
Yang, XMJ ;
Sugimura, J ;
Backdahl, J ;
Tretiakova, M ;
Qian, CN ;
Gray, SG ;
Knapp, R ;
Anema, J ;
Kahnoski, R ;
Nicol, D ;
Vogelzang, NJ ;
Furge, KA ;
Kanyama, H ;
Kagawa, S ;
Teh, BT .
ONCOGENE, 2003, 22 (43) :6810-6818
[18]   Expression profiling of renal epithelial neoplasms - A method for tumor classification and discovery of diagnostic molecular markers [J].
Young, AN ;
Amin, MB ;
Moreno, CS ;
Lim, SD ;
Cohen, C ;
Petros, JA ;
Marshall, FF ;
Neish, AS .
AMERICAN JOURNAL OF PATHOLOGY, 2001, 158 (05) :1639-1651