Genetic Instability Persists in Non-Neoplastic Urothelial Cells from Patients with a History of Urothelial Cell Carcinoma

• Published in: PloS one Vol. 9; no. 1; p. e86162
• Main Authors: de Castro Marcondes, João Paulo, de Oliveira, Maria Luiza Cotrim Sartor, Gontijo, Alisson M., de Camargo, João Lauro Viana, Salvadori, Daisy Maria Fávero
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.01.2014; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Aged, 80 and over; Alcohol; Alcohol use; Alcoholic beverages; Antineoplastic agents; Biology; Biomarkers; Bladder; Bladder cancer; Carcinoma; Carcinoma - genetics; Carcinoma - pathology; Case-Control Studies; Cell division; Cellular biology; Chromosomes; Cytogenetics; Disease control; Disease prevention; DNA damage; Epithelial Cells - metabolism; Epithelial Cells - pathology; Female; Fluorescence; Fluorescence in situ hybridization; Gene amplification; Gene expression; Genomic Instability; Habits; Humans; Hybridization analysis; Invasiveness; Male; Males; Medical diagnosis; Medicine; Micronuclei; Micronuclei, Chromosome-Defective; Micronucleus Tests; Middle Aged; Monitoring; Morbidity; Mutation; Neoplasm Grading; Neoplasm Staging; Neoplasms; Patients; Pesticides; Regression analysis; Risk Factors; Smoking; Stability; Tumors; Urinary bladder; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology; Urologic Neoplasms - genetics; Urologic Neoplasms - pathology; Urothelial cancer; Urothelium
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0086162

Bladder cancer is one of the most common genitourinary neoplasms in industrialized countries. Multifocality and high recurrence rates are prominent clinical features of this disease and contribute to its high morbidity. Therefore, more sensitive and less invasive techniques could help identify individuals with asymptomatic disease. In this context, we used the micronucleus assay to evaluate whether cytogenetic alterations could be used as biomarkers for monitoring patients with a history of urothelial cell carcinoma (UCC). We determined the frequency of micronucleated urothelial cells (MNC) in exfoliated bladder cells from 105 patients with (n = 52) or without (n = 53) a history of UCC, all of whom tested negative for neoplasia by cytopathological and histopathological analyses. MNC frequencies were increased in patients with a history of UCC (non-smoker and smoker/ex-smoker patients vs non-smoker and smoker/ex-smoker controls; p<0.001), in non-smoker UCC patients (vs non-smoker controls; p<0.01), and in smoker/ex-smoker controls (vs non-smoker controls; p<0.001). Patients with a history of recurrent disease also demonstrated a higher MNC frequency compared to patients with non-recurrent neoplasia. However, logistic regression using smoking habits, age and gender as confounding factors did not confirm MNC frequency as a marker for UCC recurrence. Fluorescent in situ hybridization analysis (using a pan-centromeric probe) showed that micronuclei (MN) arose mainly from clastogenic events regardless of UCC and/or smoking histories. In conclusion, our results confirm previous indications that subjects with a history of UCC harbor genetically unstable cells in the bladder urothelium. Furthermore, these results support using the micronucleus assay as an important tool for monitoring patients with a history of UCC and tumor recurrence.