Abnormalities of the tumour suppressor gene p53 have been shown in app
roximately 60% of advanced gastric adenocarcinomas and it has been sug
gested that the immunohistochemical finding of increased p53 expressio
n is a prognostic marker in gastric cancer. No studies of early (T1) t
umours have been reported. Over expression of p53 protein in 95 early
gastric carcinomas and in adjacent mucosa was investigated using immun
ohistochemistry with antibody CM1. Thirty five per cent of the tumours
were positive. The frequency of p53 positivity in tumours of tubular
histological type (46%) was significantly higher than that in signet r
ing tumours (10%) (p=0.006), and neoplasms that invaded deeply into th
e submucosa were more frequently positive (45%) than others (30%). Fiv
e of eight (62%) T1 tumours with lymph node metastases showed immunore
active p53. In signet ring tumours, immunopositivity correlated with t
he frequency of DNA aneuploidy. p53 Over expression was also found in
15% of 26 examples of high grade dysplasia in mucosa adjacent to invas
ive tumours. No positivity was found in intestinal metaplasia or in no
rmal mucosa. The findings show that immunocytochemically demonstrable
over expression of p53 correlates with other morphological markers of
aggressiveness in T1 gastric adenocarcinoma. The increasing frequency
of p53 immunoreactivity in the sequence of high grade dysplasia-->earl
y gastric cancer-->advanced gastric cancer supports the view that abno
rmalities of p53 are related to tumour progression in gastric carcinog
enesis.