world cancer report - iarc
world cancer report - iarc
world cancer report - iarc
Create successful ePaper yourself
Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.
Factor Alteration<br />
Tumour suppressor genes<br />
p53 60% mutation -- high-grade intraepithelial neoplasia<br />
and carcinoma<br />
APC Late in intraepithelial neoplasia-carcinoma sequence<br />
FHIT Common, early abnormalities<br />
CDKN2A (p16 INK4A ) Hypermethylation common in intraepithelial neoplasia<br />
Growth factor receptors<br />
CD95/APO/Fas Shift to cytoplasm in carcinoma<br />
EGFR Expressed in 60% of carcinomas, gene amplification<br />
c-erbB2 Late in dysplasia-carcinoma sequence, gene amplification<br />
Cell adhesion<br />
E-cadherin Loss of expression in intraepithelial and invasive carcinoma<br />
Catenins Similar loss of expression to E-cadherin<br />
Proteases<br />
UPA Prognostic factor in carcinoma<br />
Proliferation<br />
Ki-67 Abnormal distribution in high-grade intraepithelial<br />
neoplasia<br />
Membrane trafficking<br />
rab11 High expression in low-grade intraepithelial neoplasia<br />
Table 5.9 Genes and proteins involved in the development of adenocarcinoma from Barrett oesophagus.<br />
Fig. 5.79 A highly infiltrative adenocarcinoma in a<br />
Barrett oesophagus.<br />
226 Human <strong>cancer</strong>s by organ site<br />
Mutation of the p53 gene is common in<br />
the early stages of adenocarcinoma of<br />
the oesophagus (Table 5.9). The presence<br />
of a p53 mutation in Barrett<br />
mucosa and in dysplasia may precede<br />
the development of adenocarcinoma. In<br />
high-grade dysplasia, a prevalence of<br />
p53 mutations of approximately 60% is<br />
found, similar to that found in adenocarcinoma.<br />
Almost half of these are C to T<br />
transitions at dipyrimidine sites (CpG<br />
islands).<br />
Alteration in transcription of FHIT and of<br />
p16 INK4A may be early events in adenocarcinoma.<br />
In contrast, a number of<br />
other loci are altered at a relatively late<br />
stage with no obligate sequence of<br />
events. Prevalent changes (>50%) include<br />
loss of heterozygosity on chromosomes<br />
4q, 5q (several loci including APC), 17p<br />
and amplification of the gene encoding cerbB2.<br />
Molecules involved in membrane<br />
traffic, such as rab11, have been <strong>report</strong>ed<br />
to be specific for the loss of polarity<br />
(rounding-up of cell nuclei) seen in lowgrade<br />
dysplasia. In invasive oesophageal<br />
adenocarcinoma, reduced expression of<br />
the cadherin/catenin complex and increased<br />
expression of various proteases is<br />
detectable [15].<br />
Management<br />
Endoscopic ultrasonography is used to<br />
evaluate both depth of tumour infiltration<br />
and para-oesophageal lymph node<br />
involvement. In advanced carcinomas, CT<br />
and MRI give information about local and<br />
systemic spread. Tumour growth is characterized<br />
as swelling of the oesophageal<br />
wall, with or without direct invasion to surrounding<br />
organs. The primary treatment<br />
for local disease is oesophagectomy. This<br />
surgical approach is rarely curative (eventually<br />
85 to 90% of the patients die of<br />
recurrent disease) but palliation of dysphagia<br />
is an important secondary objective.<br />
Placement of a prosthetic tube or<br />
stent across the tumour stenosis (narrowing)<br />
may be indicated to restore swallowing<br />
in patients not suitable for surgery.<br />
Radiotherapy (external beam or brachytherapy)<br />
as well as multiple chemotherapeutic<br />
protocols have also been proposed<br />
(alone or combined with surgery), but<br />
these approaches are rarely curative.<br />
Palliation with radiation alone is an alternative<br />
to surgery, particularly if combined<br />
NSW, Australia<br />
USA (Whites)<br />
Netherlands<br />
Osaka, Japan<br />
Shanghai, China<br />
USA (Blacks)<br />
France<br />
Slovakia<br />
Madras, India<br />
Denmark<br />
Qidong, China<br />
Chiang Mai, Thailand<br />
5<br />
13.7<br />
13.2<br />
12<br />
11.7<br />
11.2<br />
9.1<br />
9<br />
8<br />
6.5<br />
4.2<br />
3.8<br />
0 50 100<br />
% survival, both sexes<br />
Fig. 5.80 Five-year relative survival after diagnosis<br />
of oesophageal <strong>cancer</strong>.