Upper Urothelial Carcinomas Associated with Balkan Endemic Nephropathy and Their Similarities with Upper Urothelial Carcinomas in Analgesic Nephropathy

The incidence of upper urothelial carcinomas (UUC) is even more than hundred times higher in the foci of Balkan endemic nephropathy (BEN), by investigations of our team, and others. Every tenth patient suffers from both diseases. Etiology is unknown. It would seem that BEN is a tubulointerstitial nephritis associated with urothelial malignancy. We found that apoptosis plays an important role in the early phase of BEN, similarly as in other toxic nephropathies. Petronic shows great similarity between Balkan nephropathy and analgesic nephropathy, as well as between upper urothelial carcinomas associated with both diseases. Based on investigation of grade to stage ratio in 100 tumors from our series of UUC, the upper urothelial carcinomas from BEN areas are characterized by slow growth of tumor mass in comparison to the same carcinomas outside BEN regions in former Yugoslavia and the evaluated cut-off point % cErb-B2+ cells for aggressive tumors of grade 3 or stage 2 is slightly greater for the UUC in the general population. Smaller cell population in proliferation in the UUC from BEN regions than what is detected in the UUC outside these regions may explain BEN tumor resistance to putative toxic agent effect during tumor progression in grade 2, although the same toxin has probably realized tumor induction. It would seem that the cErb-B2 (a receptor for EGF) is differently involved in the control of a cell cycle proliferation in urothelial tumor associated with BEN.