Fatty acid synthase is a predictive marker for aggressiveness in meningiomas.
Fatty acid synthase is a predictive marker for aggressiveness in meningiomas.
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脂肪酸合酶是脑膜瘤侵袭性的预测标志物。
DOI：
10.1007/s11060-012-0907-3
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Kuratsu J.
中科院分区：
文献类型：
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作者：
Makino K;Nakamura H;Hide T;Yano S;Kuroda J;Iyama K;Kuratsu J.
脑膜瘤是最常见的颅内肿瘤。虽然大多数是良性的WHO I级肿瘤，II级和III级肿瘤是侵袭性的，生存率很低。II级和III级脑膜瘤的治疗选择有限，分子靶点很少。包括糖酵解、脂肪生成和核苷酸合成在内的代谢途径的重新编程是癌细胞中生理变化的标志。由于脂肪酸合成酶（FAS），负责从头合成脂肪酸的酶，已成为几种癌症的潜在治疗靶点，我们研究了它在脑膜瘤中的作用。我们对57例I级、18例II级和III级以及6例放射诱导肿瘤的92例石蜡包埋标本进行FAS免疫组化研究。尽管与I级肿瘤（29.8%）相比，其在II级和III级脑膜瘤（62.9%）中的表达增加（卡方检验：p< 0.001），FAS在具有高MIB-1指数和浸润到周围组织的I级肿瘤中表达。所有放射诱导的脑膜瘤均表达FAS，其表达与MIB-1指数呈正相关（p< 0.005）。我们的研究结果表明，FAS表达增加反映了脑膜瘤的侵袭性，它可能是治疗不可切除或恶性肿瘤的新的治疗靶点。
Meningiomas are the most frequent intracranial tumors. Although most are benign WHO grade I tumors, grade II and III tumors are aggressive and survival is poor. Treatment options for grade II and III meningiomas are limited, and molecular targets are few. The re-programming of metabolic pathways including glycolysis, lipogenesis, and nucleotide synthesis is a hallmark of the physiological changes in cancer cells. Because fatty acid synthase (FAS), the enzyme responsible for the de-novo synthesis of fatty acids, has emerged as a potential therapeutic target for several cancers, we investigated its involvement in meningiomas. We subjected 92 paraffin-embedded samples from 57 patients with grade I, 18 with grade II and III, and six with radiation-induced tumors to immunohistochemical study of FAS. Whereas its expression was increased in grade II and III meningiomas (62.9 %) compared with grade I tumors (29.8 %) (chi-squared test:p< 0.001), FAS was expressed in grade I tumors with a high MIB-1 index and infiltration into surrounded tissues. All radiation-induced meningiomas expressed FAS and its expression was positively correlated with the MIB-1 index (p< 0.005). Our findings suggest that increased FAS expression reflects the aggressiveness of meningiomas and that it may be a novel therapeutic target for treatment of unresectable or malignant tumors.