Sorensen P H, Shimada H, Liu X F, Lim J F, Thomas G, Triche T J
Department of Pathology and Laboratory Medicine, British Columbia's Children's Hospital/University of British Columbia, Vancouver, Canada.
Cancer Res. 1995 Mar 15;55(6):1385-92.
Accurate diagnosis of primitive childhood sarcomas continues to be a formidable problem because these malignancies generally demonstrate very little morphological evidence of their tissue of origin. One of these tumor classes, the Ewing's sarcoma family of peripheral primitive neuroectodermal tumors (pPNETs), are thought to have a neural histogenesis based on evidence of neuroectodermal differentiation. Greater than 95% of pPNETs carry t(11;22) or t(21;22) chromosomal translocations which fuse the EWS gene from chromosome 22q12 in-frame with either FLI1 from chromosome 11q24 or ERG from chromosome 21q22. The pPNETs are considered to be histogenetically distinct from rhabdomyosarcomas, myogenic tumors lacking these EWS gene fusions and hypothesized to derive from immature skeletal muscle precursors. In the present study, we describe a unique set of childhood soft tissue sarcomas that show both neural and myogenic differentiation. These biphenotypic tumors express myogenic regulatory factors and muscle-specific antigens and also show neuroectodermal differentiation with ultrastructural evidence of neurosecretory granules and expression of neural-associated genes. Northern analysis and reverse transcriptase PCR reveal expression of EWS/FLI1 gene fusions in all biphenotypic sarcomas analyzed. Chimeric EWS/FLI1 transcripts and fusion proteins in these tumors are identical to those described for pPNETs. Our results provide evidence for a class of biphenotypic childhood sarcomas with myogenic and neural differentiation and suggest that these tumors may be related to the Ewing's sarcoma family of pPNETs.
准确诊断儿童原发性肉瘤仍然是一个棘手的问题，因为这些恶性肿瘤通常很少显示出其起源组织的形态学证据。其中一类肿瘤，即外周原始神经外胚层肿瘤（pPNETs）的尤因肉瘤家族，基于神经外胚层分化的证据，被认为具有神经组织发生学特征。超过95%的pPNETs携带t(11;22)或t(21;22)染色体易位，这些易位将22号染色体q12上的EWS基因与11号染色体q24上的FLI1基因或21号染色体q22上的ERG基因框内融合。pPNETs被认为在组织发生学上与横纹肌肉瘤不同，横纹肌肉瘤是缺乏这些EWS基因融合的肌源性肿瘤，推测起源于未成熟的骨骼肌前体。在本研究中，我们描述了一组独特的儿童软组织肉瘤，它们同时显示神经和肌源性分化。这些双表型肿瘤表达肌源性调节因子和肌肉特异性抗原，还显示神经外胚层分化，有神经分泌颗粒的超微结构证据和神经相关基因的表达。Northern分析和逆转录酶PCR显示，在所有分析的双表型肉瘤中均有EWS/FLI1基因融合的表达。这些肿瘤中的嵌合EWS/FLI1转录本和融合蛋白与pPNETs中描述的相同。我们的结果为一类具有肌源性和神经分化的儿童双表型肉瘤提供了证据，并表明这些肿瘤可能与pPNETs的尤因肉瘤家族有关。
