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.
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