Expression of fatty acid synthase as a prognostic indicator in soft tissue sarcomas

Abstract

Purpose: Fatty acid synthase (FAS) is a key enzyme in the de novo biosynthesis of fatty acids. Carcinoma cells are dependent on endogenous fatty acid synthesis for growth in vitro. In a subset of human cancers, elevated FAS is associated with poor prognosis; however, the expression of FAS and the relationship between FAS and prognosis in soft tissue sarcomas (STSs) have not been studied. The objective of this study is to examine the expression of FAS in STSs and determine its relationship to clinicopathological features and prognosis.

Experimental design: Sixty-four cases of STS were examined. The clinicopathological features and immunohistochemical expression of FAS and Ki-67 antigen were studied. Survival analysis was performed using the log-rank test and the Cox multivariate regression model.

Results: FAS expression was observed in 20 of 64 cases (31.3%) of STS. FAS-positive sarcomas were found in 13 of 23 malignant fibrous histiocytomas, 3 of 17 liposarcomas, 3 of 7 malignant peripheral nerve sheath tumors, and 1 extraskeletal mesenchymal chondrosarcoma. No expression of FAS was seen in the synovial sarcomas, leiomyosarcomas, or rhabdomyosarcomas that were examined. Clinicopathologically, FAS-positive tumors were significantly deep-seated (P = 0.02) and large in size (P = 0.03). FAS expression correlated with decreased disease-free survival (P = 0.006) and decreased overall survival (P = 0.003). In a multivariate analysis, expression of FAS was able to predict decreased disease-free survival but did not reach the level of significance for overall survival.

Conclusions: FAS expression is one of the predictive indicators for disease prognosis in STS.