Histologic and Molecular Characterization of Solid Pedia

准确的儿科肿瘤组织学特征是在NCI儿科肿瘤科（POB）临床试验中招募患者的必要条件。儿童实体瘤的诊断往往是困难的，需要多种诊断技术的结合。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)为参与POB临床试验的儿童肿瘤患者组织标本提供最先进的诊断(2)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(3)对病理住院医师和研究员进行儿科肿瘤病理学教学。儿科肿瘤服务是复杂的，工作人员参与了24小时服务的各个方面，包括与临床医生的现场咨询和收到病理材料后的及时评估，冷冻切片咨询，组织采购，肿瘤组织的组织学评估，用于肉瘤易位研究，以及通过POB提交的所有儿科肿瘤的手术和分子病理报告的最终签字。住院医师和研究员的教学在儿科肿瘤病例的签到和有组织的讲座（部门会议）中进行。

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.