Immunolocalisation of cytochrome P-450 3A enzymes in human breast carcinoma: Relationship with tumour differentiation and steroid receptors

Cytochrome P-450 3A enzymes belong to the most abundant subfamily of the cy tochrome P-450 system. They are predominantly found in the liver where they metabolize numerous drugs and endogenous substances such as oestrogens. Ho wever, they are also expressed by normal and tumoural extrahepatic tissues. Accordingly, immunolocalization was assessed in malignant breast rumours ( n=32) and normal counterparts, by using a monoclonal antibody that recogniz es all human CYP3A proteins. We investigated a potential relation between e xpression of CYP3A protein expression, the degree of tumour differentiation assessed by the histological grade and the proliferation index assessed by Ki-67 immunostaining. Immunodetection of CYP3A was observed in 27 of the 3 2 tumours analyzed (84%). A focal staining was also observed in the adjacen t normal breast tissue in 33% of the samples, but expression was always fai nter than in tumours. A significant negative association was found between CYP3A and the proliferation index, but there was no relation with receptor status or tumour differentiation. While CYP3A protein expression can be fou nd in normal breast tissues, these data highlight higher and more frequent CYP3A in malignant breast cells. Such expression in malignant breast cells appears inversely related to the proliferation index whereas no relation is found with tumour differentiation.