HISTOLOGIC AND MOLECULAR CHARACTERIZATION OF SOLID PEDIATRIC TUMORS

儿科实体肿瘤的准确诊断需要多种诊断技术的结合，包括逆转录聚合酶链反应（RT-PCR）。许多儿童实体瘤表现出基本的细胞遗传学异常，这与其发病机制有关。尤文氏肉瘤家族肿瘤（ESFT）和腺泡状横纹肌肉瘤（RMS）的特征在于一致的染色体易位，导致基因融合和随后形成新的嵌合基因。这些分子标志物可以通过RT-PCR或荧光原位杂交（FISH）检测，不仅可以用于建立疑难病例的诊断，而且可以了解这些肿瘤的发病机制。最近，这些融合基因的产物已经成为NCI儿科肿瘤学分支（POB）新建立的方案中的疫苗疗法的靶标。本项目的目的是：（1）提供儿科实体肿瘤的最新诊断技术（2）协助评价儿科肿瘤标本中是否存在特异性融合转录本和（3）评价分子标志物在儿科肉瘤诊断、分类和发病机制中的意义。一年来取得了以下成绩：（1）共出具儿科病理学报告150份。(2)共发布了90份RT-PCR报告。(3)采用RT-PCR和常规方法对50例小儿肉瘤进行了评价。研究表明，RT-PCR是诊断所选病例所必需的，并应结合形态学结果进行解释（4）FISH是一种非常有用的技术，以检测石蜡切片中的融合产物（5）与ESFT相比，FISH对嗅神经母细胞瘤的EWS/Fli-1融合转录本呈阴性。(6)染色体11 p酪氨酸羟化酶位点的微卫星标记有助于RMS与其他梭形细胞肉瘤的区分，但不能区分泡状和胚胎性RMS。- 小儿肉瘤，RT-PCR，分子标记，-人体组织，液体，细胞等

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 Ewings 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 150 Pediatric Pathology reports were issued. (2) A total of 90 RT-PCR reports were issued. (3) A series of 50 pediatric sarcomas were evaluated by RT-PCR and conventional methods. The study showed that RT-PCR is needed for diagnosis in selected cases and should be interpreted in conjuction with the morphlogic findings (4) FISH is a very useful technique to detect fusion products in paraffin sections (5) Olfactory neuroblastoma is negative for the EWS/Fli-1 fusion transcripts by FISH, in contrast to the ESFT. (6) Microsatellite markers at the tyrosine hydroxylase locus in chromosome 11p are helpful in the distinction of RMS from other spindle cell sarcomas, but not in the distinction of alveolar from embryonal RMS. - Pediatric sarcomas, RT-PCR, molecular markers, - Human Tissues, Fluids, Cells, etc.