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式反应(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，这与其发病机制有关。尤文斯肉瘤家族肿瘤(ESFT)和肺泡型横纹肌肉瘤(RMS)的特点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。这些分子标记可通过RT-PCR或荧光原位杂交(FISH)进行检测，不仅可用于疑难病例的诊断，还可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经成为NCI儿科肿瘤科(POB)新建立的方案中疫苗治疗的目标。本项目的目标是：(1)提供最先进的儿童实体肿瘤诊断；(2)协助评估儿童肿瘤标本中是否存在特定的融合转录本；(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。在过去的一年里，取得了以下成就：(1)共发布了150份儿科病理报告。(2)共发表RT-PCR报告90篇。(3)应用逆转录聚合酶链式反应和常规方法对50例儿童肉瘤进行检测。(4)FISH是检测石蜡切片中融合产物的一种非常有用的技术。(5)嗅神经母细胞瘤FISH检测EWS/Fli-1融合转录本为阴性，而ESFT为阴性。(6)11P染色体酪氨酸羟基酶基因微卫星标记有助于RMS与其他梭形细胞肉瘤的鉴别，但对肺泡型RMS与胚胎型RMS的鉴别作用不大。-儿科肉瘤、RT-PCR、分子标志物-人体组织、体液、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.