title: Molecular markers in upper urothelial carcinoma associated to Balkan endemic nephropathy. Aristolochic acid as the major risk factor of the worldwide disease.
abstract: The role of aristolochic acid in the etiology of Balkan endemic nephropathy (BEN) and associated upper urothelial carcinoma (UUC) was recently confirmed. The aim of this study was to determine the marker(s) specific for BEN-associated UUC. A total of 82 patients with UUC (38 from the BEN region and 44 control tumors) were included in the study. The Ki-67 index in BEN tumors correlated with the grade and multifocality (p < 0.05), but in regression analysis, only the grade of BEN tumor. The p53 index was significantly higher in BEN than in control tumors (p < 0.05), as well as the alteration of p53 (p < 0.05). BEN low-stage tumors, tumors without limphovascular invasion (LVI), and tumors of the renal pelvis had a higher p53 index than the control tumors (p < 0.05, 0.01, 0.05, respectively). The Ki-67 index was higher in control tumors with high-stage and solid growth than in BEN UUC (p < 0.050, 0.005). The Ki-67 correlated with the grade, growth, stage, LVI, and multifocality of UUC on the best way, but not with the group. In regression analysis, only multifocality of UUC had predictive influence on Ki-67 activity (p < 0.001). P53 correlated with the grade, growth, and group (p < 0.05). This investigation identifies the p53 pathway as the specific cell cycle marker involved in BEN-associated UUC.
authors.affiliation: Institute of Pathology, Faculty of Medicine, University of Nis, Serbia.
authors.forename: Ljubinka
authors.initials: L
authors.lastname: Jankovic Velickovic
authors.forename: Takanori
authors.initials: T
authors.lastname: Hattori
authors.forename: Vladisav
authors.initials: V
authors.lastname: Stefanovic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D030022:Aristolochia / Q000009:adverse effects; D034341:Aristolochic Acids / Q000009:adverse effects*; D001449:Balkan Nephropathy / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D006801:Humans; D007682:Kidney Pelvis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014513:Ureter / Q000473:pathology; D014516:Ureteral Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D055815:Young Adult
chemical_list: D034341:Aristolochic Acids; D014408:Biomarkers, Tumor; D019938:Cyclin D1; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C000614131:CDKN2A protein, human; C000228:aristolochic acid I; C508053:ERBB2 protein, human