Thioesterase II is a key enzyme which regulates the production of medium-chain fatty acids in mammary gland by hydrolyzing medium-chain acyl moieties from thioester linkage to the fatty acid synthetase. Our studies with rats and humans have shown that thioesterase II is expressed exclusively in mammary epithelial cells, an observation consistent with its role in milk fat synthesis. Immunoreactive enzyme can be detected in human breast epithelial cells regardless of their state of differentiation and also in both primary and metstatic tumors of breast epithelial origin; the enzyme is undetectable in other cell types. Experiments with an animal tumor model have shown that thioesterase II is present in the serum of rats bearing a mammary epithelial tumor but is undetectable in normal serum; the concentration in serum is proportional to tumor burden. These results indicate that the enzyme may be a useful marker for the identification of human tumors of breast epithelial origin. There are two objectives for this study: (1) to test the utility of immunohistochemical thioesterase staining in the identification and classification of human breast tumors; (2) to determine whether thioesterase II is also released into the serum of human patients bearing mammary epithelial tumors and to evaluate the potential of serum testing in human breast cancer diagnosis. Thus, in pursuit of these aims, we will prepare monoclonal anti-human thioesterase antibodies for use in both immunohistochemical and enzyme-linked immunoassay procedures. In collaboration with several pathologists, we will optimize the immunohistochemical test and will evaluate the specificity and efficacy of thioesterase staining in primary breast tumors of various types and grades and detection of metastatic tumors of breast carcinomas. We will use an animal tumor model and eventually human patients to determine whether serum thioesterase levels show a reliable correlation with tumor burden and whether a level of sensitivity can be achieved which would facilitate use in the early diagnosis, prognosis, and followup of human breast cancer. (1)
