EXPRESSION OF THE PROGESTIN-INDUCED FATTY-ACID SYNTHETASE IN BENIGN MASTOPATHIES AND BREAST-CANCER AS MEASURED BY RNA INSITU HYBRIDIZATION

We have shown previously that fatty acid synthetase (FAS) is specifically induced by progestins in human breast cancer cell lines. To test the potential value of FAS as a clinical marker in breast diseases, we measured FAS expression in frozen sections of 22 benign and 27 malignant mammary tumors using in situ hybridization with the [35S]UTP αS-labeled FAS anti-sense mRNA. The hybridized RNA was quantified with an IMSTAR computerized image analyzer. We found FAS RNA in epithelial cells, but no labeling was detected in the connective tissue. In breast cancer, we found no correlation between FAS expression and estrogen receptor and progesterone receptor concentrations or status. However, the level of FAS was significantly (P <.02) higher in premenopausal than in post-menopausal patients and increased with the grade of tumor differentiation (P <.005 between the poorly and well-differentiated tumors). In benign mastopathies, high levels of FAS RNA were found in some cysts (mostly with apo-crine metaplasia). In lobules, the FAS RNA level increased proportionally to the degree of proliferation determined by histological examination (P <.015) and correlated with the H4 histone level measured in an adjacent section using insitu hybridization (r = 0.85, P <.001). In ductal structures, a lower correlation (r = 0.64, P <.01) was found between FAS and H4 RNA levels. We conclude that FAS RNA is overexpressed in some mammary tumors and may be useful in predicting high-risk mastopathies and less aggressive breast cancers. [J Natl Cancer Inst 82:602-606, 1990] © 1990 Oxford University Press.