Increased expression of fatty acid synthase (OA-519) in ovarian neoplasms predicts shorter survival

Abstract

Certain cancers exhibit derangement of de novo fatty acid biosynthesis, manifested as overexpression and hyperactivity of the lipogenic enzyme fatty acid synthase (FAS). Correlation of elevated FAS with high tumor grade and advanced stage in primary breast, prostate, and colorectal cancers has drawn attention to the enzyme as a possible marker of poor prognosis. To find a similar utility of FAS in ovarian neoplasms, we compared FAS expression in 68 ovarian tumors with their histological features and clinical outcome. Immunohistochemical localization of FAS was observed in 48 (71%) cases in which staining was either focal (defined as positive staining in 1% to 20% of cells) or multifocal/diffuse (positive staining in >20% of cells). Most (83%) of the 48 cases were represented by endometrioid, serous, or mucinous carcinomas and malignant mixed mullerian tumors (MMMTs). In contrast, ovarian adenomas and tumors of low malignant potential (LMPs) contained little or no FAS. Association between FAS expression and histological diagnosis was statistically significant. The extent of FAS immunostaining was also predictive of prognosis. Among all patients with ovarian malignancies (including LMPs), median survival was 64.8 months, when their tumors exhibited no or focal immunostaining for FAS, as opposed to 31.2 months, when staining was multifocal/diffuse ( P = .005). Similar median survival values were obtained when cases were limited to endometrioid, serous, and mucinous carcinomas. Short-term survival at 1 and 2 years was significantly higher in patients whose tumors showed no or focal expression of FAS compared with multifocal/diffuse expression. Thus, elevated FAS may serve as an independent marker for predicting poor clinical outcome in patients with ovarian cancer.