We have studied the expression of different xenobiotic metabolizing enzymes in primary operable breast cancer of no special type. The expression of two forms of cytochrome P450, microsomal epoxide hydrolase, and three classes of glutathione S-transferase was investigated using immunohistochemistry. The tumours were characterized by consistent expression of microsomal epoxide hydrolase and by variable expression of the two forms of cytochrome P450 and the three types of glutathione S-transferase. Cytochrome P450 1A and cytochrome P450 3A were identified in 39 and 22 per cent of tumours, respectively. In each case, immunostaining was present only in areas of invasive carcinoma. Epoxide hydrolase was identified in 89 per cent of tumours and glutathione S-transferases pi, mu, and alpha were identified in 56, 65, and 44 per cent of tumours, respectively. Immunoreactivity for epoxide hydrolase and glutathione S-transferases was identified in both tumours and non-neoplastic breast tissue. The presence of different xenobiotic metabolizing enzymes may have a role in determining the intrinsic drug resistance of breast cancer to a variety of anti-cancer drugs, and the expression of these enzymes can readily be assessed using immunohistochemistry.
Background. Cytochrome P‐450, epoxide hydrolase, and glutathione S‐transferase (GST) all play a key role in the metabolism of chemical carcinogens, mutagens, and various anti‐cancer drugs. All these functionally associated enzymes might be involved in both the development of hepatocellular carcinoma and in determining the anti‐cancer drug sensitivity of such tumors. Methods. The expression of two forms of cytochrome P‐450 (P‐450 IA and P‐450 IIIA), microsomal epoxide hydrolase, and three classes of cytosolic GST (alpha, mu, and pi) have been studied immunohistochemically in human hepatocellular carcinoma. Results. The hepatocellular carcinomas were characterized by a consistently high expression of epoxide hydrolase and variable expression of the cytochromes P‐450 and GST. Cytochrome P‐450 IA and IIIA stained in 64.5% and 41.9% of the 31 hepatocellular carcinomas studied, respectively. Epoxide hydrolase was present in all tumors, and GST types alpha, pi, and mu were identified in 48.4%, 38.7%, and 74.2% of the hepatocellular carcinomas, respectively. Conclusions. This study showed that the expression of xenobiotic‐metabolizing enzymes in hepatocellular carcinoma is complex and the presence of different xenobiotic enzymes in hepatocellular carcinoma may contribute to the intrinsic drug resistance of these tumors. Cancer 1993; 71:36‐43.
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