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Expression of the Lipogenic Enzyme Fatty Acid Synthase (FAS) in Retinoblastoma and Its Correlation with Tumor Aggressiveness

¹From the Department of Pathologic Anatomy, the ²Division of Pediatric Oncology, the ⁴Unit of Epidemiology and Biostatistics, and the ⁶Ocular Division, Pediatric Hospital ("Bambino Gesù"), Research Institute, Rome, Italy; the ⁵Department of Experimental Medicine and Pathology, "La Sapienza" University, Rome, Italy; and the ³Departments of Pediatrics and the ⁷Visual Science and Neurosurgery, University of Siena, Italy.

PURPOSE. Fatty acid synthase (FAS) performs the anabolic conversion of dietary carbohydrate or protein to fatty acids. Many common human cancers express high levels of FAS, and its differential expression between normal and neoplastic tissues has led to the consideration of FAS as a target for anticancer therapy. To investigate the potential of targeting FAS in the treatment of retinoblastoma, we first determined whether FAS was activated in this human tumor. Moreover, correlation of FAS expression with tumor aggressiveness was determined.

METHODS. FAS reactivity was evaluated by immunohistochemistry in 66 retinoblastoma specimens from 65 patients. Degree of tumor differentiation, choroid invasion, optic nerve infiltration, mitotic rate, and necrosis extension were estimated. FAS expression was correlated with all these tumor characteristics by means of parametric and nonparametric statistical analyses.

RESULTS. Eighty-two percent of tumors were FAS positive. Stronger FAS expression correlated with more advanced choroid (P < 0.001) and optic nerve (P = 0.016) invasion, high mitotic index (P < 0.001), and less differentiated histology (P = 0.047). Correlation with extension of necrosis was not statistically significant. Unaffected retina was negative.

CONCLUSIONS. The data suggest that expression of FAS and fatty acid synthesis support an essential functional aspect of retinoblastoma cells, perhaps cell growth or survival. FAS activation may serve as a novel target for systemic and local antineoplastic therapy and, because it increases with tumor aggressiveness, its inhibition could represent an alternative treatment strategy in advanced and resistant retinoblastomas.

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