von Brandenstein Melanie, Puetz Katharina, Schlosser Monika, Löser Heike, Kallinowski Joachim P, Gödde Daniel, Buettner Reinhard, Störkel Stefan, Fries Jochen W U
Institute of Pathology, University Hospital of Cologne, Kerpenerstraße 62, 50924 Cologne, Germany.
Institute of General, Visceral and Minimal Invasive Surgery, Clinic Northwest, Steinbacher Hohl 2-26, 60488 Frankfurt am Main, Germany.
Dis Markers. 2015;2015:368534. doi: 10.1155/2015/368534. Epub 2015 Apr 7.
Vimentin is currently used to differentiate between malignant renal carcinomas and benign oncocytomas. Recent reports showing Vimentin positive oncocytomas seriously question the validity of this present diagnostic approach. Vimentin 3 is a spliced variant and ends with a unique C-terminal ending after exon 7 which differentiates it from the full length version that has 9 exons. Therefore, the protein size is different; the full length Vimentin version has a protein size of ~57 kDa and the truncated version of ~47 kDa. We designed an antibody, called Vim3, against the unique C-terminal ending of the Vimentin 3 variant. Using immune histology, immune fluorescence, Western blot, and qRT-PCR analysis, a Vim3 overexpression was detectable exclusively in oncocytoma, making the detection of Vim3 a potential specific marker for benign kidney tumors. This antibody is the first to clearly differentiate benign oncocytoma and the mimicking eosinophilic variants of the RCCs. This differentiation between malignant and benign RCCs is essential for operative planning, follow-up therapy, and patients' survival. In the future the usage of Vimentin antibodies in routine pathology has to be applied with care. Consideration must be given to Vimentin specific binding epitopes otherwise a misdiagnosis of the patients' tumor samples may result.
波形蛋白目前用于区分恶性肾细胞癌和良性嗜酸性细胞瘤。最近有报道称波形蛋白阳性的嗜酸性细胞瘤,这严重质疑了当前这种诊断方法的有效性。波形蛋白3是一种剪接变体,在第7外显子后以独特的C末端结尾,这使其与具有9个外显子的全长版本有所不同。因此,蛋白质大小不同;全长波形蛋白版本的蛋白质大小约为57 kDa,截短版本约为47 kDa。我们设计了一种名为Vim3的抗体,针对波形蛋白3变体独特的C末端。通过免疫组织学、免疫荧光、蛋白质印迹和定量逆转录聚合酶链反应分析,仅在嗜酸性细胞瘤中可检测到Vim3过表达,这使得检测Vim3成为良性肾肿瘤的潜在特异性标志物。这种抗体是首个能明确区分良性嗜酸性细胞瘤和肾细胞癌的嗜酸性模仿变体的抗体。恶性和良性肾细胞癌之间的这种区分对于手术规划、后续治疗和患者生存至关重要。未来在常规病理学中使用波形蛋白抗体时必须谨慎。必须考虑波形蛋白的特异性结合表位,否则可能导致对患者肿瘤样本的误诊。