Histologic and Molecular Characterization of Solid Pediatric Tumors

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。NCI的儿科肿瘤服务是复杂的，工作人员参与了24小时服务的所有方面，包括与临床医生的现场咨询，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。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（尤文氏肉瘤家族肿瘤，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）患者的神经鞘肿瘤。< BR > 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何马大学的合作研究[BR] 2。NCI-00-C-0092: filgastrim- sd /01与filgastrim（G-CSF）联合化疗治疗新诊断的肉瘤<BR bb0患者的II期随机试验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的II期随机、交叉、双盲、安慰剂对照试验NCI-02-C-0259：异基因/同基因造血干细胞移植治疗高危和复发性儿童肉瘤的初步研究[BR]。NCI-04-C-0001：顺序吉西他滨和多西他赛治疗复发性骨肉瘤或尤文氏肉瘤或不可切除或局部复发性软骨肉瘤的II期研究04-N282：儿童癌症和丛状神经纤维瘤组织微阵列分子靶点筛选和临床药物开发[BR][10]。6- hg -0134: 1型神经纤维瘤病真皮神经纤维瘤的自然历史和生物学[BR][0]。NCI-01-C-0091: p -糖蛋白抑制剂Tariquidar （XR9576）联合阿霉素、长春瑞滨或多西他赛治疗顽固性实体瘤（包括脑瘤<BR BR BR）儿童患者的I期试验和药代动力学研究NCI-02-C-0141: 7天或21天ABT-751治疗儿童难治性实体瘤<BR bb0的I期研究NCI-04-C-0080：吡非尼酮治疗患有1型神经纤维瘤病和进行性丛状神经纤维瘤的儿童、青少年和年轻人的II期临床试验NCI-05-C-0235：丙戊酸在年轻复发或难治性实体瘤或中枢神经系统肿瘤患者中的I期研究NCI-05-C-0239: Talabostat联合替莫唑胺或卡铂治疗儿童复发或难治性实体肿瘤（包括<BR BR的脑肿瘤）的I期研究NCI-06-C-0043：新辅助化疗治疗散发性和1型神经纤维瘤病相关高级别不可切除的周围神经鞘恶性肿瘤的II期试验NCI-06-C-0146：依泊替龙B类似物Ixabepilone （BMS-247550）治疗顽固性实体瘤<BR BR的儿童和年轻人的II期临床试验NCI-06-C-0233: Raf激酶和受体酪氨酸激酶抑制剂BAY 43-9006 （Sorafenib）治疗难治性实体瘤或白血病儿童的I期研究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发展（神经纤维瘤病协会开发现场奖）-我们将提供儿童肿瘤组织，并与一组其他病理学家一起使用在线系统进行阵列观察和评分来解释免疫组织化学染色。< BR > 2。免疫组化评价50例骨肉瘤组织p -糖蛋白（Pgp）表达，以获得骨肉瘤中Pgp阳性相对频率的初步数据。这些数据将有助于启动一项临床研究，该研究将解决Pgp抑制剂tariquar作为骨肉瘤患者治疗方案的可行性

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).<BR> 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. <BR>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 <BR>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 <BR> 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 <BR> 4. NCI-02-C-0259: Pilot Study of Allogeneic/Syngeneic Blood Stem Cell Transplantation in Patients With High-Risk and Recurrent Pediatric Sarcomas <BR> 5. NCI-04-C-0001: Phase II Study of Sequential Gemcitabine and Docetaxel in Patients with Recurrent Osteosarcoma or Ewings Sarcoma or Unresectable or Locally Recurrent Chondrosarcoma <BR> 6. 04-N282: Childhood Cancer and Plexiform Neurofibroma Tissue Microarray for Molecular Target screening and Clinical Drug Development <BR> 7. 06-HG-0134: Natural history and biology of dermal neurofibromas in neurofibromatosis type 1 <BR> 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 <BR> 9. NCI-02-C-0141: Phase I Study of 7-Day or 21-Day ABT-751 in Children with Refractory Solid Tumors <BR>10. NCI-04-C-0080: Phase II trial of Pirfenidone in Children, Adolescents, and Young Adults With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas <BR> 11. NCI-05-C-0235: Phase I Study of Valproic Acid in Young Patients with Recurrent or Refractory Solid Tumors or CNS Tumors <BR> 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 <BR> 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 <BR>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 <BR>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 <BR> On-going collaborative projects with the POB include:<BR>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. <BR>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. The data will help initiate a clinical study which will address the feasibility of the Pgp inhibitor tariquidar as a therapeutic regimen in patients with osteosarcoma