Nuclear and Membranous Smo Expression Is Associated with Low Tumor Grade and Stage in Renal Cell Carcinomas (RCC)
Jennifer Garbaini, Kelly-Ann Kim, Rami N Al-Rohil, Christine E Sheehan, Ronald P Kaufman, Jeffrey S Ross, Alida Hayner-Buchan. Albany Medical College, Albany, NY
Background: The hedgehog signaling pathway has been reported to be aberrantly activated in many solid tumors, including renal cell carcinoma (RCC). Smoothened (Smo) is a G protein-coupled receptor which can act as an oncogene, causing unregulated activation of the Hedgehog (Hh) pathway. The current study examines the expression of Smo in RCC.
Design: Tissue sections from 146 formalin-fixed, paraffin-embedded RCC, 119 clear cell type (CC) and 27 other types, were immunostained by an automated method (Ventana Medical Systems Inc., Tucson, AZ) using goat polyclonal Smo antibody (Santa Cruz Biotech, Santa Cruz, CA). Nuclear (nSmo), membranous (mSmo), and cytoplasmic (cSmo) immunoreactivity based on intensity and distribution was semiquantitavely scored and the results were correlated with clinical and morphologic variables.
Results: nSmo overexpression was noted in 64 (44%) tumors and correlated with low grade (54% LG vs 30% HG, p=0.005 overall; 56% LG vs 31% HG, p=0.008 CCs) and early stage (50% early vs 29% advanced, p=0.038 overall; 51% early vs 32% advanced, p=0.057 trend for CCs; 43% early vs 0% advanced, p=0.097 trend for others). mSmo overexpression was noted in 86 (59%) tumors and correlated with tumor type (69% CCs vs 15% others, p<0.0001) and low grade (60% G1 vs 70% G2 vs 63% G3 vs 30% G4, p=0.013 overall; 60% G1 vs 78% G2 vs 69% G3 vs 33% G4, p=0.01 CCs) and showed a trend toward correlation with early stage (74% I vs 56% II vs 73% III vs 29% IV, p=0.054 CCs). cSmo overexpression was noted in 123 (84%) tumors and correlated with tumor type (81% CCs vs 100% others, p=0.013). On multivariate analysis, high tumor grade (p=0.003) and advanced stage (p=0.018) independently predicted overall survival.
Conclusions: Nuclear and membranous Smo overexpression correlate with low tumor grade and early pathologic stage in RCC indicating that Smo expression may exert a favorable prognostic impact for the disease. Based on these findings, further study of Smo expression in RCC appears warranted.
Category: Genitourinary (including renal tumors)
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 108, Wednesday Morning