title: Chromosomal imbalances in successive moments of human bladder urothelial carcinoma.
abstract: OBJECTIVE
  To understand developmental characteristics of urinary bladder carcinomas (UBC) by evaluating genomic alterations and p53 protein expression in primary tumors, their recurrences, and in the morphologically normal urothelium of UBC patients.
  
  
  METHODS
  Tumors and their respective recurrences, six low-grade and five high-grade cases, provided 19 samples that were submitted to laser microdissection capture followed by high resolution comparative genomic hybridization (HR-CGH). HR-CGH profiles went through two different analyses--all tumors combined or classified according to their respective histologic grades. In a supplementary analysis, 124 primary urothelial tumors, their recurrences, and normal urothelium biopsied during the period between tumor surgical resection and recurrence, were submitted to immunohistochemical analyses of the p53 protein. During the follow-up of at least 21 patients, urinary bladder washes citologically negative for neoplastic cells were submitted to fluorescence in situ hybridization (FISH) to detect copy number alterations in centromeres 7, 17, and 9p21 region.
  
  
  CONCLUSIONS
  HR-CGH indicated high frequencies (80%) of gains in 11p12 and losses in 16p12, in line with suggestions that these chromosome regions contain genes critical for urinary bladder carcinogenesis. Within a same patient, tumors and their respective recurrences showed common genomic losses and gains, which implies that the genomic profile acquired by primary tumors was relatively stable. There were exclusive genomic alterations in low and in high grade tumors. Genes mapped in these regions should be investigated on their involvement in the urinary bladder carcinogenesis. Successive tumors from same patient did not present similar levels of protein p53 expression; however, when cases were grouped according to tumor histologic grades, p53 expression was directly proportional to tumor grades. Biopsies taken during the follow-up of patients with history of previously resected UBC revealed that 5/15 patients with no histologic alterations had more than 25% of urothelial cells expressing the p53 protein, suggesting that the apparently normal urothelium was genomically unstable. No numerical alterations of the chromosomes 7, 17, and 9p21 region were found by FISH during the periods "free-of-neoplasia." Our data are informative for further studies to better understand urinary bladder urothelial carcinogenesis.
authors.affiliation: Center for Evaluation of Environmental Impact of Human Health (TOXICAM), Department of Pathology, Botucatu Medical School, UNESP-São Paulo State University, Botucatu, SP, Brazil. merielen@fmb.unesp.br
authors.forename: Merielen Garcia
authors.initials: MG
authors.lastname: Nascimento e Pontes
authors.forename: Sara Martorelli
authors.initials: SM
authors.lastname: da Silveira
authors.forename: José Carlos de Souza
authors.initials: JC
authors.lastname: Trindade Filho
authors.forename: Silvia Regina
authors.initials: SR
authors.lastname: Rogatto
authors.forename: João Lauro
authors.initials: JL
authors.lastname: Viana de Camargo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D022981:Allelic Imbalance; D001706:Biopsy; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D002503:Centromere / Q000648:ultrastructure; D002874:Chromosome Mapping; D055028:Comparative Genomic Hybridization; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D019459:Urothelium / Q000473:pathology*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53