ENZYMES OF THE FATTY-ACID SYNTHESIS PATHWAY ARE HIGHLY EXPRESSED IN IN-SITU BREAST-CARCINOMA

Expression of high levels of fatty acid synthase (FAS), an important e nzyme in fatty acid synthesis, has been identified in a wide variety o f human carcinomas, In breast and prostate carcinoma, FAS expression a ppears to be associated with aggressive disease, Recent biochemical st udies have demonstrated that FAS expression in cancer cells connotes a ctivation of the entire fatty acid synthesis pathway leading to the pr oduction of palmitic acid, Here, we explore the immunohistochemical ex pression of FAS and human acetyl-CoA carboxylase (HACC), the rate-limi ting enzyme in fatty acid synthesis, in breast cancer progression from histologically normal breast through the development of irt situ duct and lobular carcinoma to infiltrating carcinoma, Both FAS and the M-r , 275,000 isoform of HACC are expressed in a small subset of cells in normal breast lobules and terminal ducts, Upon development of either i ii situ duct or lobular carcinoma, FAS and both isoforms of HACC are e xpressed at higher levels and in a majority of the cells. These findin gs suggest that expression of the enzymes of fatty acid synthesis are frequently altered early in the progression of human breast carcinoma.