Histologic and Molecular Characterization of Solid Pedia

儿童肿瘤的准确组织学特征对于NCI儿童肿瘤分支（POB）临床试验的患者入组是必要的。儿科实体肿瘤的诊断通常很困难，需要多种诊断技术的结合。大多数儿童实体瘤的特征在于一致的染色体易位，其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。NCI的儿科肿瘤服务很复杂，工作人员24小时参与服务的各个方面，包括与临床医生进行现场咨询，并在收到病理材料后立即进行评估，冷冻切片咨询，组织采购，肉瘤移位研究中肿瘤组织组织学评价和最终体征-所有儿科肿瘤的手术和分子病理学报告。住院医师和研究员的教学发生在儿科肿瘤病例的签出和结构化讲座（部门会议）。我们的儿科肿瘤材料由以下POB方案决定，包括儿童小圆细胞肿瘤（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）患者的神经鞘瘤。1.NCI-99-C-0125：骨肉瘤：基于组织学反应的治疗结果：POB/NCI，德克萨斯儿童医院和俄克拉荷马州大学的合作成果2. NCI-00-C-0092：在新诊断的肉瘤患者中比较filgastrim-SD/01与filgastrim（G-CSF）联合化疗的II期随机试验3。NCI-01-C-0222：法尼基转移酶抑制剂R115777治疗1型神经纤维瘤病和进行性丛状神经纤维瘤4的儿童患者的II期、随机、交叉、双盲、安慰剂对照试验。NCI-02-C-0259：高风险和复发性小儿肉瘤患者异基因/同基因造血干细胞移植的初步研究5。NCI-04-C-0001：吉西他滨和多西他赛序贯治疗复发性骨肉瘤或尤文肉瘤或不可切除或局部复发性软骨肉瘤患者的II期研究6. 04-N282：儿童癌症和丛状神经纤维瘤组织微阵列用于分子靶点筛选和临床药物开发7. 06-HG-0134：神经纤维瘤病1型中真皮神经纤维瘤的自然史和生物学。NCI-01-C-0091：Tariquidar（XR 9576）（一种P-糖蛋白抑制剂）与多柔比星、长春瑞滨或多西他赛联合治疗难治性实体瘤（包括脑肿瘤）儿科患者的I期试验和药代动力学研究9. NCI-02-C-0141：7天或21天ABT-751治疗儿童难治性实体瘤的I期研究10. NCI-04-C-0080：吡非尼酮在儿童、青少年和年轻成人1型神经纤维瘤病和进行性丛状神经纤维瘤中的II期试验11。NCI-05-C-0235：丙戊酸在复发性或难治性实体瘤或CNS肿瘤年轻患者中的I期研究12. NCI-05-C-0239：Talabostat联合替莫唑胺或卡铂治疗复发性或难治性实体瘤（包括脑肿瘤）儿科患者的I期研究13. NCI-06-C-0043：散发性和1型神经纤维瘤病相关的高度不可切除的恶性外周神经鞘瘤新辅助化疗的II期试验14。NCI-06-C-0146：伊沙匹隆（BMS-247550）（一种埃博霉素B类似物）在儿童和年轻成人难治性实体瘤中的II期试验15.

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. The pediatric tumor service at the NCI 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-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 2. NCI-00-C-0092: Phase II Randomized Trial of filgastrim-SD/01 vs. filgastrim(G-CSF) with concurrent chemotherapy in patients with newly diagnosed sarcoma 3. NCI-01-C-0222: 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 4. NCI-02-C-0259: Pilot Study of Allogeneic/Syngeneic Blood Stem Cell Transplantation in Patients With High-Risk and Recurrent Pediatric Sarcomas 5. NCI-04-C-0001: Phase II Study of Sequential Gemcitabine and Docetaxel in Patients with Recurrent Osteosarcoma or Ewing's Sarcoma or Unresectable or Locally Recurrent Chondrosarcoma 6. 04-N282: Childhood Cancer and Plexiform Neurofibroma Tissue Microarray for Molecular Target screening and Clinical Drug Development 7. 06-HG-0134: Natural history and biology of dermal neurofibromas in neurofibromatosis type 1 8. NCI-01-C-0091: Phase I Trial and Pharmacokinetic Study of Tariquidar (XR9576), a P-Glycoprotein Inhibitor, in Combination With Doxorubicin, Vinorelbine or Docetaxel in Pediatric Patients With Refractory Solid Tumors Including Brain Tumors 9. NCI-02-C-0141: Phase I Study of 7-Day or 21-Day ABT-751 in Children with Refractory Solid Tumors 10. NCI-04-C-0080: Phase II trial of Pirfenidone in Children, Adolescents, and Young Adults With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas 11. NCI-05-C-0235: Phase I Study of Valproic Acid in Young Patients with Recurrent or Refractory Solid Tumors or CNS Tumors 12. NCI-05-C-0239: Phase I study of Talabostat in Combination with Temozolomide or Carboplatin in Pediatric Patients with Relapsed or Refractory Solid Tumors, Including Brain Tumors 13. NCI-06-C-0043: Phase II Trial of Neoadjuvant Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated High Grade Unresectable Malignant Peripheral Nerve Sheath Tumors 14. NCI-06-C-0146: Phase II Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, in Children and Young Adults With Refractory Solid Tumors 15.