Histologic and Molecular Characterization of Solid Pedia

在NCI儿科肿瘤科(POB)的临床试验中，准确的儿科肿瘤的组织学特征是必要的。儿童实体肿瘤的诊断通常很困难，需要综合诊断技术。大多数儿童实体瘤的特点是一致的染色体易位，导致基因融合，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。本项目的目的是：(1)对参加POB临床试验的儿童肿瘤患者的组织标本进行最先进的诊断(2)评价分子标记在儿童肉瘤诊断、分类和发病机制中的意义(3)向住院医师和研究员讲授儿科肿瘤病理学。儿科肿瘤服务很复杂，工作人员24小时全天候覆盖服务的方方面面，包括与临床医生进行现场会诊，收到病理材料后立即进行评估，冷冻切片会诊，组织采购，用于肉瘤易位研究的肿瘤组织的组织学评估，以及通过POB提交的所有儿科肿瘤的手术和分子病理学报告的最终签字。在儿科肿瘤病例注销和结构化讲座(科室会议)中，对住院医师和研究员进行教学。 我们的儿科肿瘤材料遵循以下POB方案，包括儿童小圆形细胞肿瘤(尤文肉瘤家族肿瘤、横纹肌肉瘤和神经母细胞瘤)、骨肉瘤和各种软组织肉瘤，包括神经纤维瘤病(NF)患者中的神经鞘肿瘤。 1.NCI协议97-C-0052，转移性儿童肉瘤细胞减量治疗后疫苗驱动的自体T细胞移植扩大抗肿瘤效应的初步研究。 2.NCI方案02-C-0259，异基因造血干细胞移植在高危复发儿童肉瘤患者中的初步研究。 3.NCI方案99-C-0125，骨肉瘤：基于组织学反应的治疗结果。POB/NCI的合作努力。德克萨斯儿童医院和俄克拉荷马大学。 4.NCI方案04-C-0001，对复发性尤文氏肉瘤、骨肉瘤或无法切除或局部复发的软骨肉瘤进行吉西他滨和多西紫杉醇序贯治疗的第二阶段研究。 5.NCI议定书T99-0090，A阶段II随机，交叉。法尼基转移酶抑制剂R115777在1型神经纤维瘤病和进行性丛状神经纤维瘤儿童患者中的双盲、安慰剂对照试验。 6.NCI协议00-C-0092：在接受剂量强化化疗的新诊断的儿童和年轻人肉瘤患者中进行的一项随机试验：FIRESPRIM-SD01与FIREGRIO RIM。 与公共关系局正在进行的合作项目包括： 1.用于分子靶点筛选和儿童药物开发的儿童癌症和丛状神经纤维瘤组织微阵列的开发(神经纤维瘤协会发展网站奖)-我们将与一组其他病理学家一起，使用在线系统查看阵列和评分，贡献儿童肿瘤组织并解释免疫组织化学染色。 2.免疫组织化学方法检测50例骨肉瘤组织中P-糖蛋白(P-gp)的表达，以获得骨肉瘤中P-糖蛋白(Pgp)相对阳性率的初步数据。

Accurate histologic characterization of pediatric tumors is necessary for the enrolment of patients in the clinical trials of the Pediatric Oncology Branch (POB) at the NCI. The diagnosis of the solid pediatric tumors is often difficult and requires a combination of diagnostic techniques. Most pediatric solid tumors 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 on tissue specimens from pediatric tumor patients participating in POB clinical trials (2) to evaluate the significance of molecular markers in the diagnosis, classification and pathogenesis of pediatric sarcomas (3) to teach pathology residents and fellows pediatric tumor pathology. The pediatric tumor service is complex and the staff is involved in 24-hour coverage of all aspects of the service, including on site-consultation with clinicians and prompt evaluation of pathology material upon its receipt, frozen section consultation, tissue procurement, histologic evaluation of tumor tissue for sarcoma translocation studies and final sign-out of surgical and molecular pathology reports on all pediatric tumors submitted through POB. Teaching of residents and fellows occurs during sign-out of pediatric tumor cases and in structured lectures (departmental conferences). Our pediatric tumor material is dictated by the following POB protocols and consists of small round cell tumors of childhood (Ewing sarcoma family tumors, rhabdomyosarcoma and neuroblastoma), osteosarcoma and various soft tissue sarcomas, including nerve sheath tumors in neurofibromatosis (NF) patients. 1. NCI Protocol 97-C-0052, A Pilot Study of Autologous T Cell Transplantation with a Vaccine Driven Expansion of Anti-Tumor Effectors After Cytoreductive Therapy in Metastatic Pediatric Sarcomas. 2. NCI Protocol 02-C-0259, Pilot Study of Allogeneic Blood Stem Cell Transplantation in Patients with High Risk and Recurrent Pediatric Sarcomas. 3. NCI Protocol 99-C-0125, Osteosarcoma: Outcome of therapy based on histologic response. A collaborative effort of the POB/NCI. Texas Children's Hospital and University of Oklahoma. 4. NCI Protocol 04-C-0001, Phase II study of sequential gemcitabine followed by docetaxel for recurrent Ewing's sarcoma, osteosarcoma, or unresectable or locally recurrent chondrosarcoma. 5. NCI Protocol T99-0090, A phase II randomized, cross-over. Double-blinded, placebo-controlled trial of the farnesyltransferase inhibitor R115777 in pediatric patients with neurofibromatosis type 1 and progressive plexiform neurofibromas. 6. NCI Protocol 00-C-0092: A randomized trial of filgastrim-SD01 vs. filgastrim in newly diagnosed children and young adults with sarcoma treated with dose-intensive chemotherapy. On-going collaborative projects with the POB include: 1. the development of childhood cancer and plexiform neurofibroma tissue microarray for molecular target screening and childhood drug development (Neurofibromatosis Consortium Development Site Award)- We will contribute pediatric tumor tissues and interpret immunohistochemical staining along with a group of other pathologists using an on line system for array viewing and scoring. 2. immunohistochemical evaluation of 50 osteosarcoma tissues for P-glycoprotein (Pgp) expression in order to obtain preliminary data regarding relative frequency of Pgp positivity in osteosarcoma.