Eble JN, Sauter G., Epstein JI, Sesterhenn IA - iarc

Fig. 2.23 Infiltrative urothelial carcinoma. FISH
analysis of a human metaphase chromosome
spread showing locus specific hybridization signals
for the telomeric (green signals) and the centromeric
(red signals) regions of chromosome 1.
The chromosomes have been counterstained with
4,6-Diamidino-2-phenylindol (DAPI).
Fig. 2.22 Putative model of bladder cancer development and progression based on genetic findings. Thick
arrows indicate the most frequent pathways, dotted lines the most rare events. The typical genetic alterations
in genetically stable and unstable tumours are described in the text.
Fig. 2.25 Infiltrative urothelial carcinoma. Contribution of several oncogenes in cellular signalling pathways.
Fig. 2.24 Invasive urothelial cancer. FISH analysis
shows two copies if centromere 17 (red) and more
than 30 copies of the HER2 gene (green) reflecting
HER2 gene amplification.
expression or inactivation are summarized
below.
The TP53 gene, located at 17q23
encodes a 53kDa protein which plays a
role in several cellular processes including
cell cycle, response to DNA damage,
cell death, and neovascularization
{1089}. Its gene product regulates the
expression of multiple different genes
{2757}. Mutations of the TP53 gene,
mostly located in the central, DNA binding
portion of the gene, are a hallmark of
invasively growing bladder cancers. An
online query of the International Agency
for Research on Cancer (IARC) database
(R7 version, september 2002) at
www.iarc.fr/P53/ {1957} revealed TP53
mutations in 40-60% {1569,2619} of invasive
bladder cancers (in studies investigating
at least 30 tumours). Although
there are no specific mutational hotspots,
more than 90% of mutations have been
found in exons 4-9. Often TP53 mutations
can be detected immunohistochemically
106 Tumours of the urinary system