Grass Beate, Wachtel Marco, Behnke Silvia, Leuschner Ivo, Niggli Felix K, Schäfer Beat W
Department of Oncology, University Children's Hospital, Zurich, Switzerland.
Histopathology. 2009 Jun;54(7):873-9. doi: 10.1111/j.1365-2559.2009.03303.x. Epub 2009 May 11.
Subclassification of rhabdomyosarcoma (RMS) has clinical relevance, as the two major subclasses embryonal (ERMS) and alveolar (ARMS) rhabdomyosarcoma differ greatly in terms of aggressiveness and prognosis. However, histological analysis is not always sufficient for an unequivocal subclassification of RMS. Furthermore, clinical presentation of ARMS has been reported to mimic other tumour types, specifically lymphoma. The aim was to determine the role of four biomarkers in the diagnosis of rhabdomyosarcoma.
Recently, we identified four potential biomarkers to subclassify RMS with high sensitivity and specificity. These included epidermal growth factor receptor (EGFR) and fibrillin-2 as markers for ERMS, and AP2beta and P-cadherin as markers for translocation-positive ARMS. Here, we further validate the potential of these four markers in a second, independent patient cohort by immunohistochemistry on 80 sections of RMS biopsy specimens as well as a tissue microarray representing 18 different additional tumour types, including seven lymphomas. The combination of EGFR and fibrillin-2 was able to detect ERMS with a specificity of 76% and sensitivity of 90%. The combination of AP2beta and P-cadherin detected ARMS with a specificity of 97% and sensitivity of 90%, data very similar to our previous study. Furthermore, all lymphomas were clearly negative for AP2beta and P-cadherin.
These four biomarkers are suitable for clinical implementation in the future diagnosis of RMS.
横纹肌肉瘤（RMS）的亚分类具有临床相关性，因为胚胎型（ERMS）和腺泡型（ARMS）横纹肌肉瘤这两个主要亚类在侵袭性和预后方面差异很大。然而，组织学分析对于RMS的明确亚分类并不总是足够的。此外，据报道ARMS的临床表现可模仿其他肿瘤类型，特别是淋巴瘤。本研究旨在确定四种生物标志物在横纹肌肉瘤诊断中的作用。
最近，我们鉴定出四种潜在的生物标志物，可对RMS进行高灵敏度和特异性的亚分类。其中包括表皮生长因子受体（EGFR）和原纤蛋白-2作为ERMS的标志物，以及AP2β和P-钙黏蛋白作为易位阳性ARMS的标志物。在此，我们通过对80份RMS活检标本切片以及代表18种不同其他肿瘤类型（包括7种淋巴瘤）的组织芯片进行免疫组织化学，在第二个独立患者队列中进一步验证这四种标志物的潜力。EGFR和原纤蛋白-2的组合能够检测出ERMS，特异性为76%，灵敏度为90%。AP2β和P-钙黏蛋白的组合检测ARMS的特异性为97%，灵敏度为90%，数据与我们之前的研究非常相似。此外，所有淋巴瘤的AP2β和P-钙黏蛋白均呈明显阴性。
这四种生物标志物适用于未来RMS诊断的临床应用。
