PMID- 12474226
OWN - NLM
STAT- MEDLINE
DCOM- 20030219
LR  - 20061115
IS  - 0022-3417 (Print)
IS  - 0022-3417 (Linking)
VI  - 199
IP  - 1
DP  - 2003 Jan
TI  - Frequent genetic alterations in flat urothelial hyperplasias and concomitant 
      papillary bladder cancer as detected by CGH, LOH, and FISH analyses.
PG  - 50-7
AB  - Flat urothelial hyperplasia, defined as markedly thickened urothelium without 
      cytological atypia, is regarded in the new WHO classification as a urothelial 
      lesion without malignant potential. Frequent deletions of chromosome 9 detected 
      by fluorescence in situ hybridization (FISH) have been previously reported in 
      flat urothelial hyperplasias found in patients with papillary bladder cancer. 
      Using comparative genomic hybridization (CGH) and microsatellite analysis, these 
      hyperplasias and concomitant papillary tumours of the same patients were screened 
      for other genetic alterations to validate and extend the previous findings. 
      Eleven flat hyperplasias detected by 5-ALA-induced fluorescence endoscopy and ten 
      papillary urothelial carcinomas (pTaG1-G2) from ten patients were investigated. 
      After microdissection, the DNA of the lesions was pre-amplified using whole 
      genome amplification (I-PEP-PCR). Loss of heterozygosity (LOH) analyses were 
      performed with five microsatellite markers at chromosomes 9p, 9q, and 17p. CGH 
      was performed using standard protocols. In 6 of 11 hyperplasias and 7 of 10 
      papillary tumours, deletions at chromosome 9 were simultaneously shown by FISH, 
      LOH, and CGH analyses. There was a good correlation between FISH, LOH, and CGH 
      analyses, with identical results in 6 of 10 patients. In addition to deletions at 
      chromosome 9, further genetic alterations were detected by CGH in 9 of 10 
      investigated hyperplasias, including changes frequently found in invasive 
      papillary bladder cancer (loss of chromosomes 2q, 4, 8p, and 11p; gain of 
      chromosome 17; and amplification at 11q12q13). There was considerable genetic 
      heterogeneity between hyperplasias and papillary tumours, but a clonal 
      relationship was suggested by LOH and/or CGH analyses in 5 of 10 cases. These 
      data support the hypothesis that flat urothelial hyperplasias can display many 
      genetic alterations commonly found in bladder cancer and could therefore be an 
      early neoplastic lesion in the multistep development of invasive urothelial 
      carcinoma.
CI  - Copyright 2002 John Wiley & Sons, Ltd.
FAU - Obermann, E C
AU  - Obermann EC
AD  - Institute of Pathology and Molecular Diagnostic Unit, University of Regensburg, 
      Germany.
FAU - Junker, K
AU  - Junker K
FAU - Stoehr, R
AU  - Stoehr R
FAU - Dietmaier, W
AU  - Dietmaier W
FAU - Zaak, D
AU  - Zaak D
FAU - Schubert, J
AU  - Schubert J
FAU - Hofstaedter, F
AU  - Hofstaedter F
FAU - Knuechel, R
AU  - Knuechel R
FAU - Hartmann, A
AU  - Hartmann A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
SB  - IM
MH  - Aged
MH  - Carcinoma, Papillary/*genetics/pathology
MH  - Chromosome Deletion
MH  - Chromosomes, Human, Pair 9/genetics
MH  - Female
MH  - Genome, Human
MH  - Humans
MH  - Hyperplasia/genetics
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Loss of Heterozygosity/*genetics
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Invasiveness
MH  - Nucleic Acid Hybridization
MH  - Urinary Bladder Neoplasms/*genetics/pathology
MH  - Urothelium/*pathology
EDAT- 2002/12/11 04:00
MHDA- 2003/02/20 04:00
CRDT- 2002/12/11 04:00
PHST- 2002/12/11 04:00 [pubmed]
PHST- 2003/02/20 04:00 [medline]
PHST- 2002/12/11 04:00 [entrez]
AID - 10.1002/path.1259 [doi]
PST - ppublish
SO  - J Pathol. 2003 Jan;199(1):50-7. doi: 10.1002/path.1259.