Histologic and Molecular Characterization of Solid Pediatric Tumors

儿童实体肿瘤的准确诊断需要包括逆转录聚合酶链反应（RT-PCR）在内的多种诊断技术的结合。许多儿童实体瘤表现出基本的细胞遗传学异常，这对其发病机制有影响。尤文氏肉瘤家族肿瘤（ESFT）和肺泡横纹肌肉瘤（RMS）的特征是一致的染色体易位，导致基因融合和随后形成新的嵌合基因。这些分子标记可以通过RT-PCR或荧光原位杂交（FISH）检测到，不仅可以用于疑难病例的诊断，还可以用于了解这些肿瘤的发病机制。最近，这些融合基因的产物已成为NCI儿科肿瘤科（POB）新建立的方案中疫苗治疗的目标。本项目的目的是：(1)提供儿童实体肿瘤的最新诊断；(2)协助评估儿童肿瘤标本中是否存在特异性融合转录物；(3)评估分子标记在儿童肉瘤的诊断、分类和发病机制中的意义。一年来取得了以下成绩：(1)共出具病理报告122份。(2)共发表RT-PCR报告51份。(3)采用RT-PCR技术对72例儿童肉瘤进行了融合转录物存在与否的评估（Dagher， R. et al . Int J pediatric Hematol Oncol (in press)）。(4)在对119例小儿肿瘤病例进行评估后，Myogenin被确立为横纹肌肉瘤特异性标志物（Kumar， S等）。现代病理学2000；13:988 - 993)。

Accurate diagnosis of solid pediatric tumors requires a combination of diagnostic techniques including reverse transcription polymerase chain reaction (RT-PCR). Many pediatric solid tumors exhibit fundamental cytogenetic abnormalities that have implications in their pathogenesis. The Ewing's sarcoma family of tumors (ESFT) and alveolar rhabdomyosarcoma (RMS) are characterized by consistent chromosomal translocations which result in the fusion of genes and subsequent formation of novel chimeric genes. These molecular markers can be detected by RT-PCR or fluorescence in situ hybridization (FISH) and can be used not only to establish the diagnosis in difficult cases, but also to understand the pathogenesis of these tumors. Recently, the products of these fusion genes have become the target of vaccine therapies in newly established protocols in the Pediatric Oncology Branch (POB) at the NCI. The objective of this project is: (1) to provide state of the art diagnosis of solid pediatric tumors (2) to assist in the evaluation of pediatric tumor specimens for the presence or absence of specific fusion transcripts and (3) to evaluate the significance of molecular markers in the diagnosis, classification and pathogenesis of pediatric sarcomas. The following accomplishments have been made in the last year: (1) A total of 122 Pathology reports were issued. (2) A total of 51 RT-PCR reports were issued. (3) A series of 72 pediatric sarcomas were evaluated by RT-PCR for the presence or absence of fusion transcripts (Dagher, R. et al Int J Pediatr Hematol Oncol (in press)).(4) Myogenin was established as a rhabdomyosarcoma-specific marker, after evaluation of 119 pediatric tumor cases ( Kumar, S et al. Mod Pathol 2000; 13:988-993).