world cancer report - iarc

and intestinal metaplasia (Fig. 5.25), frequently
precede and/or accompany intestinal
type adenocarcinoma, especially in
high incidence areas. Premalignant conditions
include gastric polyps, Menetrier disease,
gastric ulcer, pernicious anaemia
(achlorydia) and previous gastric surgery
to reduce acid output [3]. H. pylori strains
containing a group of genes named cag
induce a great degree of inflammation,
and there is an association between infection
with a cag positive H. pylori strain and
the development of gastric carcinoma [5].
Gastric carcinomas are morphologically
heterogeneous, resulting in various classifications
based on histological appearance,
degree of differentiation, growth
pattern, and histogenesis [6]. The major
histological types include tubular adenocarcinoma
(Fig. 5.27), papillary adenocarcinoma,
mucinous adenocarcinoma and
signet-ring cell carcinoma. When more
than one histological type is observed
within the tumour, the diagnosis is based
on the predominant histological pattern
[7]. Based on their differentiation status,
gastric carcinomas are also classified as
Histologic type
Gene alterations Poorly-differentiated (%) Well-differentiated (%)
KRAS mutation 0 10-20
c-met
Amplification ≈ 40 ≈20
6.0 kb mRNA ≈ 80 ≈ 50
K-sam amplification 20-30 0
c-erbB2 amplification 0 20-40
Cyclin E amplification 10 10
p53 LOH/mutation ≈ 80 ≈ 60
APC LOH/mutation - 40-60
DCC LOH - 50
Cadherin, catenin deletion 50 -
CD44 abnormal transcript 100 100
Genetic instability ≈ 40 ≈10
Table 5.3 Genetic alterations in gastric carcinomas, (≈ = approximately), [15, 16].
196 Human cancers by organ site
well-differentiated adenocarcinoma (composed
of well-formed glands, often resembling
metaplastic intestinal epithelium)
and poorly-differentiated adenocarcinoma
(composed of highly irregular glands or
single cells that remain isolated).
Moderately-differentiated adenocarcinomas
show intermediate features between
the two.
Gastric carcinomas may also be classified as
diffuse and intestinal types (Laurén classification)
[8]. Intestinal type carcinoma is composed
of distinct glandular elements with
well-defined lumina, sometimes accompanied
by papillary structures or solid components.
Diffuse gastric carcinoma is characterized
by the lack of cell cohesion, and
malignant cells infiltrate the surrounding tissue
as single cells or small clusters of cells
without glandular lumina [8]. Other classification
systems are also in use.
Clinical and pathological staging of stomach
cancer is based on the TNM system (Box:
TNM, p124) in Western countries and the
Japanese classification system in Japan [9].
Most gastric carcinomas occur sporadically,
but up to 10% have an inherited familial
component [10]. Case-control studies also
suggest a small but consistent increased
risk in first-degree relatives of gastric carcinoma
patients [11]. Germline E-cadherin
(CDH1) mutations lead to an autosomal
dominant predisposition to diffuse gastric
carcinoma [12]. Gastric carcinomas may
also develop as part of the hereditary nonpolyposis
colon cancer (HNPCC) syndrome
[13] (Colorectal cancer, p198). They exhibit
intestinal type cancers and microsatellite
instability.
Loss of heterozygosity studies and comparative
genomic hybridization (CGH)
studies have shown that frequent loss or
gain occurs at chromosomal regions 1p,
1q, 3p, 4, 5q (APC locus), 6q, 7q, 9p, 17p
(p53 locus), 18q (DCC locus), and 20q
[14]. Well- and poorly-differentiated adenocarcinomas
frequently show different
genetic alterations (Table 5.3), as do diffuse
and intestinal types [15,16].
Management
Most patients diagnosed with stomach
cancer have advanced disease and the
prognosis is extremely poor with survival
rates rarely exceeding 15%. Differences in
classification of cancer lead to apparently
much higher survival rates in Japan (Fig.
5.28). Management of stomach cancer
Fig. 5.28 Five-year relative survival after diagnosis
of gastric carcinoma.