PURPOSE: Molecular characterization of renal cell carcinoma may help differentiate benign oncocytoma from malignant renal cell carcinoma subtypes and predict metastasis. Chemokines, eg IL-8 and chemokine receptors such as CXCR4 and 7, promote inflammation and metastasis. SDF-1 is a CXCR4 and 7 ligand with 6 known isoforms. We evaluated the expression of these chemokines and chemokine receptors in kidney specimens. MATERIALS AND METHODS: Using quantitative polymerase chain reaction we measured mRNA levels of IL-8, CXCR4 and 7, and SDF1 isoforms α, β and γ in a total of 166 specimens from 86 patients, including 86 tumor samples and 80 matched normal kidney samples. Mean ± SD followup was 18.9 ± 12 months (median 19.5). Renal cell carcinoma specimens included the clear cell, papillary and chromophobe subtype in 65, 10 and 5 cases, respectively, and oncocytoma in 6. A total of 17 cases were positive for metastasis. RESULTS: Median CXCR4 and 7, and SFD1-γ levels were increased twofold to tenfold. SDF1-α and β were unchanged or lower in clear cell renal cell carcinoma and papillary tumors than in normal tissue. Median SDF1-γ, IL-8, and CXCR4 and 7 were increased threefold to fortyfold in chromophobe tumors compared to oncocytoma. CXCR4 and 7 were increased in tumors less than 4 cm (mean 3,057 ± 2,230 and 806 ± 691) compared to oncocytoma (336 ± 325 and 201 ± 281, respectively, p ≤0.016). On multivariate analysis CXCR4 (p = 0.01), CXCR7 (p = 0.02) and SDF1-β (p = 0.005) were independently associated with metastasis. Combined CXCR7 plus SDF1-α and CXCR7 plus IL-8 markers showed the highest sensitivity (71% to 81%) and specificity (75% to 80%) of all individual or combined markers. CONCLUSIONS: Chemokines and chemokine receptors differentiate renal cell carcinoma and oncocytoma. Combined SDF1-α plus CXCR7 and IL-8 plus CXCR7 markers have about 80% accuracy for predicting renal cell carcinoma metastasis.
PURPOSE: Molecular characterization of renal cell carcinoma may help differentiate benign oncocytoma from malignant renal cell carcinoma subtypes and predict metastasis. Chemokines, eg IL-8 and chemokine receptors such as CXCR4 and 7, promote inflammation and metastasis. SDF-1 is a CXCR4 and 7 ligand with 6 known isoforms. We evaluated the expression of these chemokines and chemokine receptors in kidney specimens. MATERIALS AND METHODS: Using quantitative polymerase chain reaction we measured mRNA levels of IL-8, CXCR4 and 7, and SDF1 isoforms α, β and γ in a total of 166 specimens from 86 patients, including 86 tumor samples and 80 matched normal kidney samples. Mean ± SD followup was 18.9 ± 12 months (median 19.5). Renal cell carcinoma specimens included the clear cell, papillary and chromophobe subtype in 65, 10 and 5 cases, respectively, and oncocytoma in 6. A total of 17 cases were positive for metastasis. RESULTS: Median CXCR4 and 7, and SFD1-γ levels were increased twofold to tenfold. SDF1-α and β were unchanged or lower in clear cell renal cell carcinoma and papillary tumors than in normal tissue. Median SDF1-γ, IL-8, and CXCR4 and 7 were increased threefold to fortyfold in chromophobe tumors compared to oncocytoma. CXCR4 and 7 were increased in tumors less than 4 cm (mean 3,057 ± 2,230 and 806 ± 691) compared to oncocytoma (336 ± 325 and 201 ± 281, respectively, p ≤0.016). On multivariate analysis CXCR4 (p = 0.01), CXCR7 (p = 0.02) and SDF1-β (p = 0.005) were independently associated with metastasis. Combined CXCR7 plus SDF1-α and CXCR7 plus IL-8 markers showed the highest sensitivity (71% to 81%) and specificity (75% to 80%) of all individual or combined markers. CONCLUSIONS: Chemokines and chemokine receptors differentiate renal cell carcinoma and oncocytoma. Combined SDF1-α plus CXCR7 and IL-8 plus CXCR7 markers have about 80% accuracy for predicting renal cell carcinoma metastasis.
Authors: Matthias Niedermeier; Bryan T Hennessy; Zachary A Knight; Marina Henneberg; Jianhua Hu; Antonina V Kurtova; William G Wierda; Michael J Keating; Kevan M Shokat; Jan A Burger Journal: Blood Date: 2009-03-24 Impact factor: 22.113
Authors: Andrew Chi; Samir P Shirodkar; Diogo O Escudero; Obi O Ekwenna; Travis J Yates; Rajinikanth Ayyathurai; Michael Garcia-Roig; Jeffrey C Gahan; Murugesan Manoharan; Vincent G Bird; Vinata B Lokeshwar Journal: Cancer Date: 2011-09-01 Impact factor: 6.860
Authors: Mario W Kramer; Diogo O Escudero; Soum D Lokeshwar; Roozbeh Golshani; Obi O Ekwenna; Kristell Acosta; Axel S Merseburger; Mark Soloway; Vinata B Lokeshwar Journal: Cancer Date: 2010-10-19 Impact factor: 6.860
Authors: B König; F Steinbach; B Janocha; A Drynda; M Stumm; C Philipp; E P Allhoff; W König Journal: Anticancer Res Date: 1999 Mar-Apr Impact factor: 2.480
Authors: David Maussang; Azra Mujić-Delić; Francis J Descamps; Catelijne Stortelers; Peter Vanlandschoot; Marijke Stigter-van Walsum; Henry F Vischer; Maarten van Roy; Maria Vosjan; Maria Gonzalez-Pajuelo; Guus A M S van Dongen; Pascal Merchiers; Philippe van Rompaey; Martine J Smit Journal: J Biol Chem Date: 2013-08-26 Impact factor: 5.157
Authors: Yana G Najjar; Patricia Rayman; Xuefei Jia; Paul G Pavicic; Brian I Rini; Charles Tannenbaum; Jennifer Ko; Samuel Haywood; Peter Cohen; Thomas Hamilton; C Marcela Diaz-Montero; James Finke Journal: Clin Cancer Res Date: 2016-10-31 Impact factor: 12.531
Authors: Younghun Jung; Frank C Cackowski; Kenji Yumoto; Ann M Decker; Jingcheng Wang; Jin Koo Kim; Eunsohl Lee; Yugang Wang; Jae-Seung Chung; Amy M Gursky; Paul H Krebsbach; Kenneth J Pienta; Todd M Morgan; Russell S Taichman Journal: Cancer Res Date: 2018-02-05 Impact factor: 12.701
Authors: Lu Miao; Aaron K Holley; Yanming Zhao; William H St Clair; Daret K St Clair Journal: Antioxid Redox Signal Date: 2014-01-22 Impact factor: 8.401
Authors: Miguel Gosalbez; Marie C Hupe; Soum D Lokeshwar; Travis J Yates; John Shields; Muthu K Veerapen; Axel S Merseburger; Charles J Rosser; Mark S Soloway; Vinata B Lokeshwar Journal: J Urol Date: 2013-11-26 Impact factor: 7.450