Altered glutamyl-aminopeptidase activity and expression in renal neoplasms

Background: Advances in the knowledge of renal neoplasms have demonstrated the implication of several proteases in their genesis, growth and dissemination. Glutamyl-aminopeptidase (GAP) (EC. 3.4.11.7) is a zinc metallopeptidase with angiotensinase activity highly expressed in kidney tissues and its expression and activity have been associated wtih tumour development. Methods: In this prospective study, GAP spectrofluorometric activity and immunohistochemical expression were analysed in clear-cell (CCRCC), papillary (PRCC) and chromophobe (ChRCC) renal cell carcinomas, and in renal oncocytoma (RO). Data obtained in tumour tissue were compared with those from the surrounding uninvolved kidney tissue. In CCRCC, classic pathological parameters such as grade, stage and tumour size were stratified following GAP data and analyzed for 5-year survival. Results: GAP activity in both the membrane-bound and soluble fractions was sharply decreased and its immunohistochemical expression showed mild staining in the four histological types of renal tumours. Soluble and membrane-bound GAP activities correlated with tumour grade and size in CCRCCs. Conclusions: This study suggests a role for GAP in the neoplastic development of renal tumours and provides additional data for considering the activity and expression of this enzyme of interest in the diagnosis and prognosis of renal neoplasms.We wish to thank Arantza Perez (UPV/EHU) for her technical contribution to this study. The authors also thank Ana Abascal, Alicia Esteve and Mar Gonzalez, lab technicians at the Department of Pathology, Cruces University Hospital, for their excellent immunohistochemical work. This work was supported by grants from the Basque Government (IT8-11/13), the University of the Basque Country UPV/EHU (UFI 11/44, EHUA 12/15) and the Gangoiti Barrera Foundation. We want to particularly acknowledge the patients enrolled in this study for their participation and the Basque Biobank for Research-OEHUN for this collaboration