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

Fig. 1.20 Clear cell renal cell carcinoma. Survival
curves by grade for patients with clear cell renal
cell carcinoma. From C.M. Lohse et al. {1532}.
Fig. 1.19 Clear cell RCC. Note deletion of 3p as the only karyotype change.
However, recent data give evidence for
other putative tumour suppressor genes
at 3p, e.g. RASSF1A at 3p21 {1789} and
NRC-1 at 3p12 {1562}.
Chromosome 3p deletions have been
observed in very small clear cell tumours of
the kidney and are regarded as the initial
event in clear cell cancer development
{2107,2109,2925}. Inactivation of the VHL
gene has consequences for VHL protein
function. The VHL protein negatively regulates
hypoxia-inducible factor, which activates
genes involved in cell proliferation,
neo-vascularization, and extracellular
matrix formation {642,1310,1828}.
Fig. 1.22 Clear cell RCC. VHL deletion, there are two
signals in red (chromosome 3), and one signal in
green (VHL gene). FISH expression.
Clonal accumulation of additional genetic
alterations at many chromosomal locations
then occurs in renal cancer progression
and metastasis {247,339,958,
1218,1754,2109,2179,2344,2345}. High
level gene amplifications are rare in clear
cell renal cell carcinoma {1754}.
Individual chromosomal gains and losses
have been analyzed for an association
with patient prognosis. Chromosome
9p loss seems to be a sign of poor prognosis
{1754,2341}. Losses of chromosome
14q were correlated with poorer
patient outcome, high histologic grade
and high pathologic stage {226,1080,
2344,2849}. LOH on chromosome 10q
around the PTEN/MAC locus have been
frequently detected and were related to
poor prognosis {2722}.
Expression levels of many genes have
been studied in clear cell RCC. The role
of p53 expression in renal cell carcinoma
is controversial. A few studies suggest
that p53 overexpression is associated
with poor prognosis and with sarcomatoid
transformation {1932,1939,2164,
2659}. High expression levels of bFGF,
VEGF, IL-8, MMP-2, MMP-9, vimentin,
MHC class II and E-cadherin may be
important for development and/or progression
{320,1472,1892,2391,2437}.
Expression of epidermal growth factor
receptor (EGFR) is frequent in renal cell
carcinoma and has been proposed as
prognostic parameter {1755}. Whereas
Fig. 1.21 Clear cell carcinoma. Survival of patients
depends on the presence and extent of sarcomatoid
differentiation, ranging from no differentiation
(n=326), to sarcomatoid differentiation in 50% (n=31) of tumour area. From H.
Moch et al. {1753}. Copyright © 2000 American
Cancer Society. Reprinted by permission of Wiley-
Liss, Inc., a subsidiary of John Wiley & Sons, Inc.
amplification of the EGFR gene on chromosome
7p13 is a major cause for EGFR
expression in brain tumours, this pathway
is uncommon in renal cell carcinoma
{1756}. HER2/neu amplifications are rare
or absent in renal cell carcinoma
{2339,2799}.
cDNA array analysis of clear cell renal
carcinoma showed complex patterns of
gene expression {1759,2887}. It has
been shown that the integration of
expression profile data with clinical data
could serve to enhance the diagnosis
and prognosis of clear cell RCC {2551}.
Clear cell renal cell carcinoma
25