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Volume 11, Pages 1699-1711
Clinical Study

Pro- and Antiapoptotic Markers in Upper Tract Urothelial Carcinoma Associated with Balkan Endemic Nephropathy

1Institute of Pathology, Faculty of Medicine, University of Nis, 18000 Nis, Serbia
2Department of Pathology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2121, Japan
3Public Health Institute, Nis, Serbia
4Institute of Nephrology, Faculty of Medicine, University of Nis, Boulevard Dr Zoran Djindjic 81, 18000 Nis, Serbia

Received 4 July 2011; Accepted 6 September 2011

Academic Editor: Anthony Atala

Copyright © 2011 Ljubinka Jankovic-Velickovic et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The role of aristolochic acid in the etiology of Balkan endemic nephropathy (BEN) and associated upper-tract urothelial carcinoma (UTUC) has been recently confirmed. The aim of this study was to determine apoptosis-related marker(s) specific for BEN-associated UTUC. Present investigation included 105 patients with UTUC, 44 from BEN region and 61 control tumors. Altered expression of Survivin was more often present in BEN UTUC with high grade and solid growth ( 𝑃 < 0 . 0 0 5 ; 𝑃 < 0 . 0 5 ) than in control tumors. Significantly lower expression of proapoptotic marker Bax was found in BEN tumors with high grade, high stage, necrosis, and without metaplastic change ( 𝑃 < 0 . 0 5 ; 0.05; 0.05; 0.05) compared to control tumors with the same features. Group (BEN-related/control), stage, growth pattern, and caspase 3 activity were significantly associated with the expression of Bax ( 𝑃 = 0 . 0 0 2 , 0.034, 0.047, 0.028, resp.,). This investigation identifies Bax as specific marker of BEN-associated UTUC. Decrease of pro-apoptotic protein Bax together with alteration of Survivin may be indicative for specific disturbances of intrinsic apoptotic pathway in UTUC arising in endemic areas.