Kapur Payal, Rakheja Dinesh, Roy Lonnie C, Hoang Mai P
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9073, USA.
Mod Pathol. 2005 Aug;18(8):1107-12. doi: 10.1038/modpathol.3800395.
Mammalian fatty acid synthase is a multifunctional enzyme complex involved in de novo synthesis of saturated fatty acids, and inhibitors of fatty acid synthase are being evaluated as potential therapeutic agents. Increased fatty acid synthase expression has been demonstrated in subsets of malignancies, including colon, breast, endometrium, prostate and ovarian carcinomas, and recently malignant melanomas. We evaluated the immunohistochemical expression of fatty acid synthase in 155 cutaneous melanocytic lesions. They included 30 congenital nevi, 19 compound nevi, 40 Spitz nevi, 48 primary melanomas, and 18 metastatic melanomas. Fatty acid synthase expression was stronger in malignant melanomas in comparison to conventional nevi and Spitz nevi, and was the highest for metastatic melanoma. Of the primary malignant melanomas, mean fatty acid synthase scores were significantly greater for Clark levels IV and V compared to Clark levels I and II (P<0.001). In addition, melanomas with Breslow thickness 0.75-1.50 mm and >1.50 mm showed significantly higher mean fatty acid synthase scores compared with those with Breslow thickness <0.75 mm (P=0.013 and <0.001, respectively). Of interest, congenital melanocytic nevi also showed strong fatty acid synthase expression, similar to that seen in metastatic melanoma. This may represent persistence of or regression to a fetal phenotype since normal fetal tissues are known to express high levels of fatty acid synthase.
哺乳动物脂肪酸合酶是一种参与饱和脂肪酸从头合成的多功能酶复合物，脂肪酸合酶抑制剂正作为潜在治疗药物进行评估。脂肪酸合酶表达增加已在包括结肠癌、乳腺癌、子宫内膜癌、前列腺癌和卵巢癌以及最近的恶性黑色素瘤等恶性肿瘤亚组中得到证实。我们评估了155例皮肤黑素细胞病变中脂肪酸合酶的免疫组化表达。它们包括30例先天性痣、19例复合痣、40例Spitz痣、48例原发性黑色素瘤和18例转移性黑色素瘤。与传统痣和Spitz痣相比，恶性黑色素瘤中脂肪酸合酶表达更强，转移性黑色素瘤中表达最高。在原发性恶性黑色素瘤中，Clark分级IV级和V级的平均脂肪酸合酶评分显著高于Clark分级I级和II级（P<0.001）。此外，Breslow厚度为0.75 - 1.50 mm和>1.50 mm的黑色素瘤的平均脂肪酸合酶评分显著高于Breslow厚度<0.75 mm的黑色素瘤（分别为P = 0.013和<0.001）。有趣的是，先天性黑素细胞痣也显示出强烈的脂肪酸合酶表达，类似于转移性黑色素瘤中的表达。这可能代表向胎儿表型的持续或回归，因为已知正常胎儿组织表达高水平的脂肪酸合酶。
