ELEVATED EXPRESSION OF FATTY-ACID SYNTHASE AND FATTY-ACID SYNTHETIC ACTIVITY IN COLORECTAL NEOPLASIA

Expression of the primary enzyme catalyzing the synthesis of fatty aci ds, ie, fatty acid synthase (FAS), and ex vivo fatty acid synthetic ac tivity were examined in colorectal epithelium and neoplasms, including the relationship to tumor progression and prognosis. Immunohistochemi stry for FAS showed only faint staining of native colorectal mucosa, b ut increased expression was found in all sporadic adenomas (n=18), ade nomas associated with familial adenomatous pol yposis (n=7), hyperplas tic polyps (n=3), dysplasias arising in ulcerative colitis (n=17), and colorectal carcinomas (n=130) including 11 with contiguous adenomas. The intensity of staining was strong In 53% of carcinomas, intermediat e in 38%, and weakin 9%. Activity of the fatty acid synthetic pathway measured by label ing of six surgical specimens with [U-C-14]acetate w as 2- to 7-fold higher in colorectal carcinomas than adjacent native m ucosa (P=0.006) and 6-to 16-fold higher than serosal fat (P=0.01). Act ivity correlated with imtnunohistochemical expression (Spearman's rank correlation coefficient =0.85; P <0.001). There was no statistically significant association between patient survival and FAS staining inte nsity of carcinomas, Our study shows that FAS is expressed in all colo rectal neoplasms and there is a concomitant increase in fatty acid syn thesis, FAS may therefore represent a potential therapeutic target.