Histologic and Molecular Characterization of Solid Pediatric Tumors

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。NCI的儿科肿瘤服务是复杂的，工作人员24小时覆盖服务的方方面面，包括现场咨询临床医生和收到病理材料后立即评估，冷冻切片咨询，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-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大学的合作努力2.NCI-00-C-0092：在新诊断的肉瘤患者中进行丝裂霉素-SD/01与丝裂霉素(G-CSF)的II期随机试验3.NCI-01-C-0222：II期随机、交叉、双盲、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安慰剂对照试验4.NCI-02-C-0259：高危和复发儿童肉瘤患者异基因/同基因血液干细胞移植的初步研究5.NCI-04-C-0001：复发性骨肉瘤或尤文氏肉瘤或无法切除或局部复发的软骨肉瘤患者的序贯吉西他滨和多西紫杉醇的II期研究6.04-N282：儿童癌症和丛状神经纤维组织瘤患者用于分子靶点筛选和临床药物开发的微阵列7.06-HG-0134：18型神经纤维瘤病中真皮神经纤维瘤的自然历史和生物学。NCI-01-C-0091：他立克定(XR9576)的I期试验和药代动力学研究，P-糖蛋白抑制剂联合阿霉素、长春瑞滨或多西紫杉醇治疗儿童难治性实体肿瘤包括脑肿瘤9.NCI-02-C-0141：儿童难治性实体肿瘤7天或21天ABT-751的I期研究10.NCI-04-C-0080：儿童、青少年Pirfenidone的II期试验11.NCI-05-C-0235：丙戊酸在年轻复发或难治性实体肿瘤或中枢神经系统肿瘤患者中的I期研究12.NCI-05-C-0239：他拉博斯特联合替莫唑胺或卡铂治疗儿童复发或难治性实体肿瘤的I期研究，包括脑肿瘤13.NCI-06-C-0043：散发性和神经纤维瘤病1型相关的高级别恶性周围神经鞘瘤新辅助化疗的II期试验14.NCI-06-C-0146：伊克沙比隆(BMS-247550)的II期试验，一种Epothilone B类似物，儿童和年轻人的难治性实体肿瘤15.NCI-06-C-0233：Raf Kinase和受体酪氨酸激酶抑制剂Bay 43-9006(Sorafenib)在儿童难治性实体肿瘤或难治性白血病NCI-07-C-0040中的I期研究NCI-07-C-0040：单抗HGS-ETR2(Lexatumab)在儿童难治性实体肿瘤患者中的I期试验正在进行的与POB合作的项目包括：1.儿童癌症和丛状神经纤维瘤组织微阵列的分子靶点研究筛查和儿童药物开发(神经纤维瘤病协会发展网站奖)-我们将捐赠儿科肿瘤组织，并与一组其他病理学家一起使用在线系统进行阵列查看和评分。2.采用免疫组织化学方法对参加HGS-ETR2临床方案的儿童肉瘤组织进行细胞凋亡相关蛋白的检测。

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. NCI-06-C-0233: A Phase I Study of the Raf Kinase and Receptor Tyrosine Kinase Inhibitor BAY 43-9006 (Sorafenib) in Children with Refractory Solid Tumors or Refractory Leukemias NCI-07-C-0040: A Phase I Trial of Monoclonal Antibody HGS-ETR2 (Lexatumumab) in Patients with Refractory Pediatric Solid Tumors 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 solid pediatric sarcoma tissues from patients enrolled in the HGS-ETR2 clinical protocol for apoptosis-related proteins.