Erythrocyte fatty acids and fatty acid synthase expression in benign and malignant prostate

A40 Objectives: Dysregulation of fatty acid synthase (FAS) may have early influences on prostate carcinogenesis. FAS, a multienzyme that catalyzes de novo fatty acid synthesis, is highly expressed in prostate cancer, and is correlated with greater disease severity. In normal cells FAS transcription is regulated by nutrients, including fatty acids. However, in cancer cell lines FAS transcription becomes autonomously regulated. In the current analyses, we address the hypothesis that FAS is overexpressed in malignant as opposed to benign prostate tissue and that FAS expression is associated with variations in erythrocyte (ERC) fatty acid concentrations.
 Methods: In this translational study, we used population methods to investigate a biologic mechanism for cancer progression. Information on diet and other risk factors was obtained from consented patients referred for clinical suspicion of prostate cancer. Blood specimens were obtained prior to prostate biopsy, and ERC fatty acid concentrations were determined using GC-MS. Sections of residual formalin-fixed, paraffin-embedded tissues were prepared, including benign tissue from biopsy-positive cases and biopsy-negative controls and when present, invasive adenocarcinoma. FAS expression was assessed by standard immunohistochemistry, and the slides were scored for percent of glands stained, average staining intensity and range of staining intensity. Summary scores were calculated and the difference in FAS expression between tissues was determined by t-test. General linear regression was used to model the association between FAS expression in benign, surrounding benign and malignant tissue and ERC fatty acid levels. Final regression models were adjusted for age, total caloric intake and PSA.
 Results: Data were analyzed for 148 controls with biopsies negative for tumor and 70 incident prostate cancer cases; 61 of whom had adequate tumor and benign tissue for comparison. Mean FAS staining was significantly greater in malignant tissue (8.54 +/- 4.29 as compared to both surrounding benign (3.46 +/-2.86) and benign tissue from biopsy negative controls (3.28 +/- 2.71, p Conclusions: Our results show that there was no association between ERC fatty acid levels and prostate tumor tissue FAS expression. However, ERC fatty acid levels were associated with alterations of FAS expression in the benign component of men with cancer.
 Overall, our findings suggest that in benign tissue FAS expression may still be regulated via nutritional controls providing a mechanism by which fatty acids may alter risk of progression of prostatic epithelium from the benign to the malignant state.