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Detection of N-Glycolyl GM3 Ganglioside in Neuroectodermal Tumors by Immunohistochemistry: An Attractive Vaccine Target for Aggressive Pediatric Cancer

机译:免疫组织化学法检测神经外胚层肿瘤中N-乙二醇基GM3神经节苷脂:侵袭性小儿癌的有吸引力的疫苗靶标

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The N-glycolylated ganglioside NeuGc-GM3 has been described in solid tumors such as breast carcinoma, nonsmall cell lung cancer, and melanoma, but is usually not detected in normal human cells. Our aim was to evaluate the presence of NeuGc-GM3 in pediatric neuroectodermal tumors by immunohistochemistry. Twenty-seven archival cases of neuroblastoma and Ewing sarcoma family of tumors (ESFT) were analyzed. Formalin-fixed, paraffin-embedded tumor samples were cut into 5? μ m sections. The monoclonal antibody 14F7, a mouse IgG1 that specifically recognizes NeuGc-GM3, and a peroxidase-labeled polymer conjugated to secondary antibodies were used. Presence of NeuGc-GM3 was evident in 23 of 27 cases (85%), with an average of about 70% of positive tumors cells. Immunoreactivity was moderate to intense in most tumors, showing a diffuse cytoplasmic and membranous staining, although cases of ESFT demonstrated a fine granular cytoplasmic pattern. No significant differences were observed between neuroblastoma with and without NMYC oncogene amplification, suggesting that expression of NeuGc-GM3 is preserved in more aggressive cancers. Until now, the expression of N-glycolylated gangliosides in pediatric neuroectodermal tumors has not been investigated. The present study evidenced the expression of NeuGc-GM3 in a high proportion of neuroectodermal tumors, suggesting its potential utility as a specific target of immunotherapy.
机译:N-糖基化神经节苷脂NeuGc-GM3已在诸如乳腺癌,非小细胞肺癌和黑色素瘤等实体瘤中描述,但通常在正常人细胞中未检出。我们的目的是通过免疫组织化学评估NeuGc-GM3在小儿神经外胚层肿瘤中的存在。分析了27例神经母细胞瘤和尤因肉瘤家族肿瘤(ESFT)的档案病例。将福尔马林固定的,石蜡包埋的肿瘤样品切成5?微米切片。使用了单克隆抗体14F7,特异性识别NeuGc-GM3的小鼠IgG1和与第二抗体偶联的过氧化物酶标记的聚合物。在27例病例中有23例(85%)明显存在NeuGc-GM3,平均约70%为阳性肿瘤细胞。在大多数肿瘤中,免疫反应性是中等至强烈的,表现出弥漫性的细胞质和膜性染色,尽管ESFT病例显示出良好的颗粒状细胞质模式。在有和没有NMYC癌基因扩增的神经母细胞瘤之间未观察到显着差异,这表明NeuGc-GM3的表达在更具侵略性的癌症中得以保留。迄今为止,尚未研究小儿神经外胚层肿瘤中N-糖基化神经节苷脂的表达。本研究证明了NeuGc-GM3在神经外胚层肿瘤中的高表达,表明其作为免疫治疗的特定靶标的潜在用途。

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