Abstract
The cytochromes P450 have a central role in the oxidative activation and detoxification of a wide range of xenobiotics, including many carcinogens and several anti-cancer drugs. Thus the cytochrome P450 enzyme system has important roles in both tumour development and influencing the response of tumours to chemotherapy. Stomach cancer is one of the commonest tumours of the alimentary tract and environmental factors, including dietary factors, have been implicated in the development of this tumour. This type of tumour has a poor prognosis and responds poorly to current therapies. In this study, the presence and cellular localization of several major forms of P450, CYP1A, CYP2E1 and CYP3A have been investigated in stomach cancer and compared with their expression in normal stomach. There was enhanced expression of CYP1A and CYP3A in stomach cancer with CYP1A present in 51% and CYP3A present in 28% of cases. In contrast, no P450 was identified in normal stomach. The presence of CYP1A and CYP3A in stomach cancer provides further evidence for the enhanced expression of specific forms of cytochrome P450 in tumours and may be important therapeutically for the development of anti-cancer drugs that are activated by these forms of P450.
Highlights
We have investigated the expression of P450 in stomach cancer and compared it with normal stomach and different types of intestinal metaplasia, the major precursor lesion of stomach cancer
CYP1A immunoreactivity was identified in 51% (20) of tumours, whereas immunoreactivity for CYP3A was identified in 28% (11) of tumours (Table 1)
CYPIA and CYP3A were identified in both histological types of stomach cancer (Table 1), and there was no correlation between the histological type or tumour stage (Table 2) and British Journal of Cancer (1998) 77(7), 1040-1044
Summary
Samples of tissue were obtained from gastrectomy specimens submitted to the Department of Pathology, University of Aberdeen. A total of 39 tumours were studied consisting of 24 tumours from men and 15 tumours from women (age range 38-84 years). Blocks of tumour and non-tumour tissue were fixed in neutral-buffered formalin for 24 h and embedded in wax. One section from each block was stained with haematoxylin and eosin for histology. All the tumours were primary adenocarcinomas of stomach. The tumours were classified according to Lauren (1965), and there were 12 (31%) tumours of diffuse type and 27 (69%) tumours of intestinal type. TNM staging of tumours showed that there were five (13%) stage la tumours, three (8%) stage lb tumours, 15 (39%) stage 2 tumours, 15 (39%) stage 3 tumours and one (3%) stage 4 tumour
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