Subcellular Localization of Gli-1 Correlates with Histologic Type, Grade and Stage of Renal Cell Carcinoma (RCC)
Rami N Al-Rohil, Kelly-Ann Kim, Jennifer Garbaini, Christine E Sheehan, Ronald P Kaufman, Jeffrey S Ross, Alida Hayner-Buchan. Albany Medical College, Albany, NY
Background: Hedgehog (Hh) pathway signaling is important in embryonic development and stem cell renewal and leads to activation of glioma associated oncogene 1 (Gli-1), which transcriptionally regulates target genes. Although Hh pathway reactivation has been described in RCC, Gli-1 protein expression has not been evaluated as a prognostic factor for the disease.
Design: Tissue sections from 145 formalin-fixed, paraffin-embedded RCCs (119 Clear Cell [CC], and 26 other types) were immunostained by an automated method (Ventana Medical Systems Inc., Tucson, AZ) using goat polyclonal GLI-1 antibody (Santa Cruz Biotech, Santa Cruz, CA). Nuclear (nGli), membranous (mGli), and cytoplasmic (cGli) immunoreactivity based on intensity and distribution was semiquantitavely scored and the results were correlated with clinical and morphologic variables.
Results: nGli-1 overexpression was noted in 54 (57%) tumors and correlated with tumor type (42% CCs vs 15% others, p=0.008), low grade (80% G1 vs 54% G2 vs 29% G3 vs 0% G4, p<0.0001 overall; 80% G1 vs 59% G2 vs 26% G3 vs 0% G4, p<0.0001 CCs), early stage (52% I vs 31% II vs 38% III vs 0% IV, p=0.038 CCs) and lengthened survival (44% alive vs 20% expired, p=0.008 overall; 51% alive vs 21% expired, p=0.004 CCs). mGli-1 overexpression was noted in 83 (57%) tumors and correlated with tumor type (69% CCs vs 4% others, p<0.0001) and low grade (100% G1 vs 72% G2 vs 57% G3 vs 15% G4, p<0.0001 overall; 100% G1 vs 79% G2 vs 69% G3 vs 20% G4, p<0.0001 CCs) and showed a trend toward correlation with lengthened survival (74% alive vs 58% expired, p=0.08 CCs). cGli-1 overexpression was noted in 69 (48%) tumors and correlated with tumor type (85% others vs 39% CCs, p<0.0001) and high grade (80% G4 vs 52% G3 vs 37% G2 vs 0% G1, p=0.001 overall, 73% G4 vs 49% G3 vs 29% G2 vs 0% G1, p=0.002 CCs). On multivariate analysis, high tumor grade (p=0.003) and advanced stage (p=0.018) independently predicted overall survival.
Conclusions: nGli-1 and mGli-1 overexpression characterize CC RCC and are associated with favorable prognostic features in RCC including low tumor grade, early pathologic stage and longer survival. In contrast, cGli-1 overexpression is associated with non-CC RCC and unfavorable prognostic factors such as high grade. Further study of the subcellular expression of Gli-1 in RCC is indicated.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 138, Monday Morning