[Molecular genetics of urinary bladder cancer progression].
Extensive cytogenetic and molecular analyses have recently helped to gain a much better understanding of the biology of urinary bladder cancer. Early studies had suggested two different pathways of bladder cancer development, one characterized by chromosome 9 losses and the other by p53 mutations. Subsequent studies have greatly expanded these data. Overall, there is compelling evidence for two entirely different bladder tumor entities. One entity consists of genetically unstable tumors that have many cytogenetic alterations, including p53 alterations in about 50% of the cases. Other cytogenetic alterations that can be found frequently in these tumors are deletions of 8p, 9p, 11p, 11q, and Y as well as gains of 1q, 8q, 17q, and 20q. More than 20 chromosomal regions can undergo high level DNA amplification including 17q21 (HER-2/neu). Phenotypically, these tumors are characterized by a high degree of cytological atypia. Their growth pattern can be non-invasive flat (carcinoma in situ), non-invasive papillary (pTaG3) or invasive (papillary or solid). The other, "benign" bladder cancer entity is composed of tumors with a low level of genetic instability, a low number of cytogenetic alterations, and absence of p53 mutations. Morphologically, these tumors are papillary non-invasive neoplasms with a low degree of cytological atypia. Progression to invasively growing carcinoma is extremely rare.


CONCLUSIONS
Molecular studies have revealed profound genetic differences between invasive and non-invasive bladder cancers. This argues against the previously used combination of pTa and pT1 tumor stages as "superficial bladder cancer". The high frequency of genetic alterations in invasive carcinomas enables a markedly improved detection of bladder cancer cells in voided urine using fluorescence in situ hybridization (FISH) assays.
Sauter
G
G
Institut für Pathologie, Universität Basel, Schoenbeinstrasse 40, CH-4031 Basel, Schweiz.
Simon
R
R
Bubendorf
L
L
Mihatsch
M
M
D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D018450:Disease Progression; D006801:Humans; D008967:Molecular Biology / Q000379:methods; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*