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JOURNAL OF PATHOLOGY, VOL.
178: 475 (1996)
LETTER TO THE EDITOR
THE SEQUENTIAL ACCUMULATION OF GENETIC ALTERATIONS
CHARACTERISTIC OF THE COLORECTAL ADENOMA-CARCINOMA
SEQUENCE DOES NOT OCCUR BETWEEN GASTRIC ADENOMA AND
ADENOCARCINOMA
In a recent issue of the Journal of Pathology (Vol. 176,
No. 3, 249-258), Maesawa et al. reported that APC
mutations were found in 20 per cent of gastric adenomas
and 1.4 per cent of cases of gastric cancer, while the p53
gene was mutated in 35 per cent of cases of gastric
carcinoma but not in gastric adenoma. Judging from
these observations and loss of heterozygosity (LOH) at
the DCC locus, they concluded that the adenomacarcinoma sequence does not exist for gastric carcinogenesis, as indicated by the title of their paper.
In contrast to their study, we have recently reported
that by using PCR-SSCP and direct sequencing analysis, APC mutations are detected in 25 per cent (2/8) of
gastric cancer cell lines, 42 per cent (5/12) of gastric
adenomas and 6 per cent (146) of intestinal metaplasia.'
Moreover, we found APC mutations in 41 per cent
(7/14) of very well differentiated adenocarcinomas by
means of RNase protection analyses.2 Interestingly,
both MKN-7 and MKN-28 cancer cell lines sharing
APC mutations are derived from well differentiated
adenocarcinomas of the stomach.' We previously
reported that the p53 gene was mutated in 30 per cent
(3/10) of gastric adenomas and in 56 per cent (9/16) of
primary gastric carcinomas including early gastric
cancer.334 Moreover, we sometimes experience the
development of adenocarcinoma from the long-term
follow-up of adenomatous lesions in daily surgical
pathology diagnostic practice. Thus, we believe that at
least some cases of gastric cancer can develop through
an adenomaxarcinoma sequence. Indeed, a case of
tubular adenoma with severe atypia containing p53
mutation and microsatellite instability developed a well
differentiated adenocarcinoma from the adenoma 3
years after the initial diagno~is.~
There are two possible explanations for the differences
between our results on the incidence of APC and p53
mutations in gastric adenoma and cancer and those of
$2 1996 by John Wiley & Sons, Ltd.
Maesawa et al., and in particular, their failure to detect
mutation of the p53 gene in gastric adenoma and their
recognition of only one case of APC mutation in gastric
cancer. The first explanation concerns the use of different criteria for the histological diagnosis of gastric
adenoma. Figure 1 in their paper, a gastric adenoma
with severe dysplasia, would be viewed in our study as a
well differentiated adenocarcinoma. Moreover, a gastric
adenoma with moderate dysplasia has a possibility of
adenocarcinoma. The second explanation may lie in
differences in the molecular techniques used for detecting genetic mutations. The use of SSCP analysis alone
frequently brings about false-negative results even if
in vitro, although this point was addressed in their
Discussion. In our opinion , the data on APC and p53
mutation reported by Maesawa et al. are underestimated
and their claim in the title of their manuscript is not fully
substantiated.
EIICHITAHARA
AND HIROSHI
YOKOZAKI
First Department of Pathology
Hiroshima University School of Medicine
1-2-3 Kasumi, Minami-ku
Hiroshima 734, Japan
REFERENCES
1.
2.
3.
4.
5.
Nishimura K, Yokozaki H, Haruma K, Kajiyama G, Tahara E. Alterations
of the APC gene in carcinoma cell lines and ;Irecancerous lesions of the
stomach. Int J Oncol 1995; 7: 587-592.
Nakatsuru S, Yanagisawa A, Ichii S, et a/. Somatic mutation of the APC
gene in gastric cancer: frequent mutations in very well differentiated
adenocarcinoma and signet-ring cell carcinoma. Hum Mol Genet 1992; 1:
559--563.
Todo H, Yokozaki H, Haruma K, Kajiyama G, Tahara E. pS3 mutations in
gastric adenomas. Virchows Arch B [Cell Pothol] 1993; 63: 191-195.
Yokozaki H, Kuniyasu H, Kitadai Y, ef al. p53 point mutations in primary
human gastric carcinomas. J Cancer Res CIin Oncol 1992; 119 67-70.
Semba S, Yokozaki H, Yasui W, Tahara E. Microsatellite instability in
precancerous lesions and adenocarcinoma of the stomach. Cancer Suppl (in
press).
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