Expression of fatty acid synthase as a prognostic marker in triple negative breast cancer.

Abstract

Abstract Abstract #1082 Background: Fatty acid synthase (FAS), the key enzyme required for fatty acid biosynthesis, is minimally expressed in most normal human tissue. Recent studies have demonstrated that hyperactivity or overexpression of FAS is a common feature in subset of sex steroid-related tumors, including breast carcinoma. Moreover, up-regulation of FAS gene expression is more pronounced in more advanced tumors, and strong expression of FAS seems to be associated with a poor prognosis of breast cancer. We examined the expression of FAS in invasive breast carcinomas to investigate the prognostic value of FAS expression in a large cohort of breast carcinomas with long term follow up data.
 Methods: Five hundred and ninety six cases of invasive breast carcinoma, retrospectively selected from 1987-2004, were incorporated into tissue microarrays (TMAs). We performed immunohistochemical stains for FAS, ER, progesterone receptor (PR) and Her-2/neu. Triple-negative breast cancers (TNBCs) were defined as those with ER-, PR- and Her-2/neu-negative results. The results of immunohistochemical stains were correlated with other known clinicopathologic parameters and evaluated for an effect on estimating prognosis.
 Results: The mean age at diagnosis was 47.2 (ranges 20∼85 years) with a mean tumor size of 2.5cm (ranges 0.4∼11cm). The expression of FAS was positive in 437 (73.3%) cases. There was no significant correlation between the expression of FAS and clinicopathologic characteristics of the tumor (age, tumor size, lymph node metastasis and lymphovascular invasion) (p>0.05). FAS expression was inversely correlated with histologic grade (p=0.009) and positively correlated with the expression of ER (p<0.001), PR (p<0.001) and Her-2/neu (p<0.001). One hundred thirty eight of 596 cases (23.1%) were TNBCs. FAS-expressing breast invasive carcinomas had a higher tendency to have triple-negative phenotype when compared to FAS-negative cancers (p<0.001) with a mean follow up of 72.3 months, there was no significant survival difference according to the FAS expression (p>0.05). However, FAS-positive group showed shorter disease free survival (DFS) (p=0.014) and overall survival (OS) (p=0.021) than FAS-negative group in patients with TNBC.
 Conclusion: This study showed that FAS expression is strongly associated with the expression of hormonal receptors and Her-2/neu in invasive breast carcinomas. Especially FAS could be a potential prognostic marker in TNBCs. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1082.