Subcellular Localization of DC-SCRIPT Correlates with Histologic Type, Grade and Stage of Renal Cell Carcinomas (RCC)
Kelly-Ann Kim, Jennifer L Garbaini, Rami N Al-Rohil, Christine E Sheehan, Ronald P Kaufman, Jeffrey S Ross, Alida Hayner-Buchan. Albany Medical College, Albany, NY
Background: Dendritic cell specific transcript (DC-SCRIPT) is a novel protein first discovered in dendritic cells encoded by an 8-kb mRNA transcription co-regulator which binds to multiple hormones and plays a key role in physiologic processes including cell growth and differentiation. Although previously linked to clinical outcome in breast cancer, DC-SCRIPT has not been previously studied as a prognostic factor for RCC.
Design: Tissue sections from 146 formalin-fixed, paraffin-embedded RCCs (119 clear cell type [CC] and 27 other types) were immunostained by an automated method (Ventana Medical Systems Inc., Tucson, AZ) using goat anti-human DC-SCRIPT/ZNF366 antibody (R&D Systems, Minneapolis, MN). Cytoplasmic and membranous immunoreactivity based on intensity and distribution was semiquantitavely scored and the results were correlated with clinical and morphologic variables.
Results: Cytoplasmic DC-SCRIPT overexpression was noted in 46 (32%) tumors and correlated with tumor type (87% papillary vs 24% CCs vs 38% others p<0.0001), high grade (60% G4 vs 42% G3 vs 14% G2 vs 0% G1, p<0.0001 overall; 53% G4 vs 39% G3 vs 10% G2 vs 0% G1, p<0.0001 CCs), and advanced stage (43% IV vs 26% III vs 60% II vs 26% I, p=0.022 overall; 43% IV vs 23% III vs 56% II vs 14% I, p=0.002 CCs). Membranous DC-SCRIPT overexpression was noted in 82 (56%) tumors and correlated with tumor type (61% CCs vs 33% others p= 0.008) and low grade (60% G1 vs 63% G2 vs 65% G3 vs 25% G4, p=0.013 overall; 60% G1 vs 67% G2 vs 69% G3 vs 20% G4, p=0.006 CCs). There was no significant coexpression of cytoplasmic and membranous immunoreactivity. On multivariate analysis, high tumor grade (p=0.003) and advanced stage (p=0.018) independently predicted overall survival.
Conclusions: The association of cytoplasmic DC-SCRIPT immunostaining with non-clear cell histology and high tumor grade and stage, and membranous DC-SCRIPT with clear cell histology and low tumor grade supports recent studies that associate different biological functions of proteins with their subcellular localization. The associations of DC-SCRIPT expression in RCC with tumor type, grade and stage suggest that this biomarker has both potential diagnostic and prognostic significance in RCC and warrants further study.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 137, Monday Morning