Fli-1 protein, a member of the ETS family of DNAbinding transcription factors, is involved in cellular proliferation and tumorigenesis. Approximately 90% of Ewing's sarcoma/primitive neuroectodermal tumors (ES/PNET) have a specific translocation, t(11;22)(q24;q12), which results in fusion of EWS to Fli-1, and production of an EWS-Fli-1 fusion protein. We have recently shown that immunohistochemistry for the carboxy terminal of Fli-1 protein is sensitive and highly specific for the diagnosis of ES/PNET. In our earlier study we noted that among normal tissues only endothelial cells and small lymphocytes expressed Fli-1. Fli-1 expression in vascular neoplasms has not been previously studied. Formalin-fixed paraffin-embedded tissue from 54 vascular tumors and 75 nonvascular tumors were immunostained for Fli-1 (1:120, Sc 356, Santa Cruz Biotechnology, Santa Cruz, CA), after steam heat-induced epitope retrieval. Only cases with >10% of cells showing nuclear staining were accepted as positive. Cases without positive internal controls (endothelium and small lymphocytes) were not scored. Positive internal controls were present in 122 of 129 cases (95%). One vascular tumor (Kaposi's sarcoma) and 7 nonvascular tumors (2 epithelioid sarcomas and 5 carcinomas) without internal controls were not scored. Fli-1 was expressed by 50 of 53 vascular tumors scored (94%), including 20 of 22 angiosarcomas, 11 of 12 hemangioendotheliomas, 7 of 7 hemangiomas, and 12 of 12 Kaposi's sarcomas. In contrast, Fli-1 expression was absent in the 68 nonvascular tumors scored (0 of 68), including 16 sarcomas, 7 melanomas, and 45 carcinomas. The results of this study strongly suggest a role for Fli-1 as a novel marker of both benign and malignant vascular tumors. The sensitivity (94%) and specificity (100%) of Fli-1 with regards to the cases evaluated in this study equal or exceed those of the established vascular markers, CD31, CD34, and von Willebrand factor. As the first nuclear, rather than cytoplasmic or membranous marker of endothelium, Fli-1 immunostaining also generally lacks cytoplasmic staining artifacts that are the result of endogenous peroxidases or biotin.

译文

:Fli-1蛋白是ETS DNA结合转录因子家族的成员,参与细胞增殖和肿瘤发生。约90%的尤因肉瘤/原始神经外胚层肿瘤(ES / PNET)具有特定的易位t(11; 22)(q24; q12),这导致EWS与Fli-1融合并产生EWS-Fli -1融合蛋白。我们最近显示,Fli-1蛋白羧基末端的免疫组织化学对ES / PNET的诊断是敏感和高度特异性的。在我们的早期研究中,我们注意到在正常组织中只有内皮细胞和小淋巴细胞表达Fli-1。 Fli-1在血管肿瘤中的表达以前尚未进行过研究。在蒸汽热诱导的抗原决定簇回收后,对来自54个血管肿瘤和75个非血管肿瘤的福尔马林固定石蜡包埋的组织进行Fli-1(1:120,Sc 356,Santa Cruz Biotechnology,Santa Cruz,CA)的免疫染色。只有细胞> 10%表现出核染色的病例才被视为阳性。没有阳性内部对照(内皮和小淋巴细胞)的病例没有评分。 129例病例中有122例(95%)存在阳性内部对照。没有内部对照的1个血管肿瘤(卡波西肉瘤)和7个非血管肿瘤(2个上皮样肉瘤和5个癌)均未评分。 Fli-1在53个评分为血管的肿瘤中表达50个(94%),包括22个血管肉瘤中的20个,12个血管内皮瘤中的11个,7个血管瘤中的7个和12个卡波济肉瘤中的12个。相比之下,评分的68例非血管肿瘤(68例中的0例)不存在Fli-1表达,包括16例肉瘤,7例黑素瘤和45例癌。这项研究的结果强烈暗示Fli-1作为良性和恶性血管肿瘤的新标志物的作用。对于本研究中评估的病例,Fli-1的敏感性(94%)和特异性(100%)等于或超过已建立的血管标志物CD31,CD34和von Willebrand因子。作为内皮的第一个核标记而不是细胞质或膜质标记,Fli-1免疫染色通常还缺少由于内源性过氧化物酶或生物素导致的细胞质染色伪影。

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