Gastric carcinoma is the most common malignant cancer
in the Korean population (1) and one of the most frequent
cancers in the world (2). Cancer is caused by the accumulation
of genetic alterations such as the activation of oncogenes and
inactivation of tumor suppressor genes (3). Gastric adenocar-
cinoma, especially of the intestinal type, is believed to arise
via a multistage process that includes chronic gastritis, gas-
tric atrophy, intestinal metaplasia, and finally dysplasia (4).
Intestinal metaplasia is classified into complete (I) and in-
complete (II & III) types depending on the secreted mucin
and mucosal characteristics, and these subtypes may exist con-
comitantly in a patient (5, 6). Intestinal metaplasia has long
been considered to play an important role in the development
of gastric carcinoma. Type III incomplete intestinal metapla-
sia was found to be more common in the mucosa of gastric
carcinoma than in the mucosa of chronic gastritis and greater
number of genetic mutations developed in incomplete meta-
plasia (6-9). The rate of evolution into gastric carcinoma was
4.58 times higher in type III intestinal metaplasia than in
type I intestinal metaplasia (10). These findings suggest that
incomplete intestinal metaplasia carry a higher risk for devel-
opment of gastric carcinoma than complete intestinal meta-
plasia. However, several studies did not show the relation
between type III intestinal metaplasia and gastric carcinoma
(11, 12). Therefore, further studies are necessary to determine
the role of the subtypes of intestinal metaplasia as a marker
for gastric carcinoma.
The mutation of the p53 gene is one of the most represen-
tative genetic abnormalities in gastric carcinoma. p53 muta-
tioncould also be observed in intestinal metaplasia with 2.5-
50% incidence reported (13-15). The mutation was more
commonly observed in incomplete intestinal metaplasia than
in complete intestinal metaplasia.
Microsatellite instability (MSI) is a mutator phenotype that
occurs through a loss of the mismatch repair system in cells,
and contribute to the generation of cancer by inducing muta-
tions of oncogenes and tumor suppressor genes (16, 17). In
gastric carcinoma, MSI is noted in the early stages of cancer
development and is shown in 13-44% of cases (18-20). The
frequency of MSI in intestinal metaplasia was variable, rang-
ingfrom 0% to 48% (18, 21-24).
However, these reports made their comparison on different
specimens from different patients. There have been few reports
that studied these genetic abnormalities according to the sub-
typesof intestinal metaplasia in a single patient.
The present study was aimed to investigate the potential
implication of the subtype of intestinal metaplasia in the rela-
tionship between intestinal metaplasia and gastric carcinoma
by comparing the mutations of the p53 gene and MSI in the
complete type (type I) intestinal metaplasia and those in the
Sung Soo Kim, Choon Sang Bhang,
Ki Ouk Min*, Hiun Suk Chae,
Sang Wook Choi, Chang Don Lee,
Keun Woo Lim
�, In Sik Chung, Doo Ho Park
Division of Gastroenterology, Department of Internal
Medicine, Department of Clinical Pathology*, and
Department of Surgery
Catholic University of Korea, Seoul, Korea
�, College of Medicine,
Address for correspondence
Doo Ho Park, M.D.
Division of Gastroenterology, Department of Internal
Medicine, Kangnam St. Mary's Hospital, 505
Banpo-dong, Seocho-gu, Seoul 137-040, Korea
Tel : +82.2-590-1341, Fax : +82.2-590-2387
E-mail : email@example.com
*This research was supported by grants from the
Korea Research Foundation (KRF-2000-003-F00099).
J Korean Med Sci 2002; 17: 490-6
Copyright � The Korean Academy
of Medical Sciences
p53 Mutations and Microsatellite Instabilities in the Subtype of
Intestinal Metaplasia of the Stomach
To investigate the potential implication of the subtype of intestinal metaplasia in
the progression to the gastric carcinoma, we analyzed the mutations of the p53
gene and microsatellite instability (MSI) both in the complete type (type I) and in
the sulphomucin-secreting incomplete type (type III) intestinal metaplasia locat-
ed adjacent to the gastric carcinoma. p53 mutations were observed in 13.3% of
type I, in 6.6% of type III intestinal metaplasia, and in 40% of gastric carcinoma.
The difference between p53 mutations observed in type I and type III intestinal
metaplasia was not statistically significant. No identical mutation of the p53 gene
was found in the intestinal metaplasia and carcinoma specimens from the patients.
There was no case of intestinal metaplasia showing MSI. In gastric carcinomas,
MSI was observed in six cases (40%). The cases harboring BAT-26 instability
did not have the mutation of the p53 gene. These data suggest that intestinal meta-
plasia adjacent to gastric carcinoma, irrespective of its subtype, do not have the
genetic alterations as showing in their carcinoma tissues.
Key Words : Intestines; Metaplasia; Subtype, Genes p53; Mutation; Microsatellite Repeats
Received : 6 February 2002
Accepted : 29 April 2002
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