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The alterations of four genes (APC, K-ras, p53, and
DCC) which are characteristic of the colorectal
adenoma-carcinoma sequence were studied in gastric
adenomas and adenocarcinomas.
In gastric carcinomas, the rarity of K-ras mutations
and the frequency of pS3 mutations and DCC loss of
heterozygosity (LOH) have also been described by other
investigators with incidences similar to ours.24 Frequent
mutations of APC are reportedly restricted to certain
histological types: very well differentiated adenocarcinoma and signet-ring cell c a r ~ i n o m a Well
. ~ to moderately differentiated adenocarcinomas, which constitute
the great majority of differentiated adenocarcinomas of
the stomach, did not carry APC m u t a t i o i i ~ . ~The
difference in the incidences of APC mutations in adenomas and adenocarcinomas of the stomach reported by
Tahara and by ourselves might indeed have resulted
from differences in the histological criteria used, as they
suggest. Methodological underestimation, however, is
unlikely because we were able to detect frequent APC
mutations in colorectal carcinomas by the same SSCP
procedure.' Furthermore, other lines of evidence have
suggested that APC is not the true target of Sq-LOH in
other than colorectal carcinoma^.^.^
In gastric adenoma, APC mutations occurred at an
incidence of 20 per cent (6/30), but alterations of K-ras,
pS3, and DCC were absent or rare.' In addition, our
recent microsatellite and allelotype analyses have
revealed no evidence for the adenoma-carcinoma
sequence in gastric carcinogenesis, because the incidence
of LOH did not exceed 10 per cent at any of the 39
microsatellite loci covering each autosomal chromosome
arm, including those at which differentiated adenocarcinomas exhibited frequent LOH.lO." Tohdo et a1.I2
reported that 30 per cent (3/10) of gastric adenomas
carried pS3 mutations. However, two of the three were
silent mutations which did not contribute to carcinogenesis. If gastric adenoma progresses to carcinoma, why do
few silent mutations occur in gastric carcinoma?
A case of well differentiated adenocarcinoma arising
from tubular adenoma is cited to emphasize the existence of the adenoma-carcinoma sequence in the stomach. We have experience of the co-existence of a.denoma
1996 by John Wiley & Sons, Ltd.
and adenocarcinoma in the stomach, but in our experience these tumours usually develop apart from each
other. In addition the so-called 'carcinoma in adenoma',
which is very common in the colon, is quite rare in the
For these reasons, we reaffirm our conclusion that the
adenoma-carcinoma sequence is not the major pathway
of carcinogenesis in the stomach.
Department of' Pathology
Iwate Medical University
School of Medicine
Uchimuru 19-1, 020 Morioka
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