German Cancer Consortium (DKTK), Clinical Cooperation Unit Neuropathology, German Cancer Research Center, DKFZ, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Acta Neuropathol. 2014 Apr;127(4):565-72. doi: 10.1007/s00401-014-1246-6. Epub 2014 Jan 25.
Malignant peripheral nerve sheath tumors (MPNST) derive from the Schwann cell or perineurial cell lineage and occur either sporadically or in association with the tumor syndrome neurofibromatosis type 1 (NF1). MPNST often pose a diagnostic challenge due to their frequent lack of pathognomonic morphological or immunohistochemical features. Mutations in the NF1 tumor suppressor gene are found in all NF1-associated and many sporadic MPNST. The presence of NF1 mutation may have the potential to differentiate MPNST from several morphologically similar neoplasms; however, mutation detection is hampered by the size of the gene and the lack of mutational hot spots. Here we describe a newly developed monoclonal antibody binding to the C-terminus of neurofibromin (clone NFC) which was selected for optimal performance in routinely processed formalin-fixed and paraffin-embedded tissue. NFC immunohistochemistry revealed loss of neurofibromin in 22/25 (88 %) of NF1-associated and 26/61 (43 %) of sporadic MPNST. There was a strong association of neurofibromin loss with deletions affecting the NF1 gene (P < 0.01). In a series of 256 soft tissue tumors of different histotypes NFC staining showed loss of neurofibromin in 2/8 myxofibrosarcomas, 2/12 (16 %) pleomorphic liposarcomas, 1/16 (6 %) leiomyosarcomas, and 4/28 (14 %) unclassified undifferentiated pleomorphic sarcomas. However, loss of neurofibromin was not observed in 22 synovial sarcomas, 27 schwannomas, 23 solitary fibrous tumors, 14 low-grade fibromyxoid sarcomas, 50 dedifferentiated liposarcomas, 27 myxoid liposarcomas, 13 angiosarcomas, 9 extraskeletal myxoid chondrosarcomas, and 7 epitheloid sarcomas. Immunohistochemistry using antibody NFC may substantially facilitate sarcoma research and diagnostics.
恶性外周神经鞘瘤 (MPNST) 来源于施万细胞或神经外膜细胞谱系，既可以散发性发生，也可以与肿瘤综合征神经纤维瘤病 1 型 (NF1) 相关发生。由于其经常缺乏特征性的形态学或免疫组织化学特征，MPNST 通常构成诊断挑战。NF1 肿瘤抑制基因的突变存在于所有 NF1 相关和许多散发性 MPNST 中。NF1 突变的存在有可能将 MPNST 与几种形态相似的肿瘤区分开来；然而，由于基因的大小和缺乏突变热点，突变检测受到阻碍。在这里，我们描述了一种新开发的针对神经纤维瘤蛋白 C 末端的单克隆抗体 (克隆 NFC)，该抗体在常规处理的福尔马林固定和石蜡包埋组织中表现出最佳性能。NFC 免疫组化显示，在 25 例 NF1 相关 MPNST 中有 22 例（88%）和 61 例散发性 MPNST 中有 26 例（43%）存在神经纤维瘤蛋白丢失。神经纤维瘤蛋白丢失与影响 NF1 基因的缺失密切相关（P<0.01）。在一组不同组织学类型的 256 种软组织肿瘤中，NFC 染色显示在 8 例黏液纤维肉瘤中有 2 例（26%）、12 例多形性脂肪肉瘤中有 2 例（16%）、16 例平滑肌肉瘤中有 1 例（6%）和 28 例未分类的未分化多形性肉瘤中有 4 例（14%）存在神经纤维瘤蛋白丢失。然而，在 22 例滑膜肉瘤、27 例神经鞘瘤、23 例孤立性纤维肿瘤、14 例低度纤维黏液肉瘤、50 例去分化脂肪肉瘤、27 例黏液样脂肪肉瘤、13 例血管肉瘤、9 例骨外黏液样软骨肉瘤和 7 例上皮样肉瘤中未观察到神经纤维瘤蛋白丢失。使用抗体 NFC 的免疫组化可能大大促进肉瘤的研究和诊断。
