The expression of fatty acid synthase (FASE) is an early event in the development and progression of squamous cell carcinoma of the lung

Correlation of elevated levels of the lipogenic enzyme, fatty acid synthase (FASE), with advanced stages of some cancers has drawn attention to this e nzyme as a possible marker of poor prognosis. Because recent studies have s hown that cancer cells are dependent on fatty acid synthetic activity and p harmacologic inhibitors of this enzyme are selectively cytotoxic to cancer cells, expression of FASE also may provide a potential target for intervent ion in the neoplastic process.:To determine the potential usefulness of exp ression of FASE in the neoplastic process of the lung, we evaluated its pat tern of expression immunohistochemically in archival specimens from 60 huma n lung specimens with squamous cell cancer (SCC) and associated "preneoplas tic" lesions compared with its expression in the normal bronchial epitheliu m of 60 noncancer specimens. The expression of FASE was significantly big-h er in SCC associated uninvolved bronchial epithelium (mean = 0.40 +/- 0.03, median = 0.38) compared with its expression in the bronchial epithelium of noncancer specimens (mean = 0.18 +/- 0.02, median = 0.16) indicating its e arly expression. We also observed a statistically significant step-wise inc rease in FASE expression from SCC associated uninvolved bronchial epitheliu m (mean = 0.40 +/- 0.03, median = 0.38) to epithelial hyperplasia (0.58 +/- 0.04, median = 0.57) to SCC (1.53 +/- 0.06, median = 1.50). The results su ggested that expression of FASE is an early event in the development and pr ogression of SCC of the lung. The inhibition of fatty acid synthesis by inh ibiting. enzymatic function with metabolic analogues may be a useful strate gy in the treatment of SCCs. The expression of FASE in early lesions such a s SCC associated uninvolved bronchial epithelium and epithelial hyperplasia might also provide a potential means for intervention early in the neoplas tic process in the lung or even preventing their malignant transformation t o invasive carcinomas. Copyright (C) 2000 by W.B. Saunders Company.