Dystroglycan expression correlates with tumor grade and with outcome in renal cell carcinoma patients

Abstract

15554 Background: The dystroglycan (DG) complex is a transmembrane glycoprotein that forms a continuous link from the extracellular matrix to the actin cytoskeleton. Deregulated expression of DG has been reported in a variety of human malignancies and related to tumor differentiation and aggressiveness. Methods: In this study, the expression of the a-subunit of DG was evaluated by immunostaining in a series of 125 renal cell carcinomas (RCCs) and its relation with disease progression and cancer-specific survival was evaluated. Results: to date, median follow-up is 19 months (range 1–96). We found that a-DG expression was lost in a significant fraction of tumors (66%) with 18% being the mean percentage of positive cells (median = 0; range = 0–80%). Loss of DG staining correlated with higher tumor grade (p=0.039) but not with tumor stage or size. Recurrence (p=0.014) and death (p=0.041) from RCCs were significantly more frequent in patients whose tumors displayed reduced staining for DG compared with patients whose tumors were positive for a-DG expression. Kaplan-Meier analysis showed a significant separation between high vs low a-DG expression for both disease-free (p=0.0094) and overall (p=0.0023) survival. In a multivariate analysis, loss of a-DG expression was the only independent risk predictor for recurrence (HR=6.509, p=0.0012) and death (HR=4.701, p=0.012) from RCCs when tumor size as well as tumor grade and stage were included in the model. Conclusions: These findings demonstrate that loss of a-DG expression, which correspond to loss a functional DG complex, is a frequent event in human renal tumorigenesis and is associated with an aggressive phenotype of the disease. They also suggest that evaluation of DG expression has the potential to offer important prognostic information and warrant further studies to better understand the role(s) of this molecule in term of renal cancer development and as a new prognostic marker for RCC patients. No significant financial relationships to disclose.