world cancer report - iarc

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