Charalampos Dokos, Athanassios Tragiannidis
2nd Pediatric Clinic, Hematology-Oncology Unit, AHEPA Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

Introduction
Sarcomas are a significant subject of musculoskeletal oncology. The diagnosis and theraepeutic management concerns not only orthopedic surgeons, but also pediatricians and general physicians. In particular, the Ewing sarcoma is a very aggressive tumor of bone that occurs in children age 5-23 years (average age of onset 16 years). It is the second most malignant tumor of the musculoskeletal system after osteosarcoma and concerns 3% of all cancer cases in children.

The Ewing's sarcoma is distinguished among others because of its mesechymal origin. Histomorphological  and immunohistochemical studies have shown that Ewing's sarcoma is caused by the transformation of undifferentiated cells of neural origin but not in relation with neuroblastoma. Histologically Ewing's sarcoma consists of round tumor cells neuroectodermal origin. The presence of Homer-Wright rosettes is a usuall index of Ewing sarcoma, indicating the differentiation of neural tissue. There is a tiny whitish cytoplasm due to the formation of the rich in glycogen. James Ewing in 1921 observed and described for the first time Ewing's sarcoma as an invasive endothelial volume of bone.

 

Molecular - genetic background: the search for molecular markers of Ewing sarcoma
Molecular and genetic level indicates the particular "nature" of sarcoma Ewing. Especially cytogenetic studies in children with Ewing's sarcoma showed reciprocal translocations in the 11th and 22nd chromosome of the human genome. These transfers occurring in 90% of cases with sarcoma Ewing, directly linked to the presence of primarily neuroectodermal (primitive neuroectodermal tumor - PNET) and Askin tumor. Genetic studies on fragments of these chromosomal translocations showed that the genes EWS and FLI1 are responsible for the appearance of the tumor. Aurias and co. (1983) showed that 85% of cases of Ewing's sarcoma have a specific transloaction of t (11; 22) (q24; q12), which is a fusion of EWS transcripts of the genes that encode transcription factors ETS (FLI1) of 90 -95% of patients or ERG (5-10% of patients). It seems that the translocation is strong predictor for the usual type of Ewing sarcoma, where we have the fusion of exon 7 of EWS with exon 6 of FLI1.
The clarification of these prognostic indicators is extremely important. The clinician who comes into contact with patients with Ewing's sarcoma should evaluate these indicators in terms not only at the stage of disease diagnosis but also at the outcome of chemotherapy. Other researchers have suggested the loss of p53 transcription factor (25% of cases) and increased expression of Ki-67. These changes are associated with rapid development of sarcoma and low response to chemotherapy. All these indicators can be used for the evaluation of chemotherapeutic protocols and progress of the patient. In children with Ewing's sarcoma should be karyotypic study, to identify the fusion of the fragments and chimeric peptides EWS-FLI1 or EWS-ERG. The research on the expression of specific genes in Ewing's sarcoma has a significant effect. None the less believed that their expression may be associated with the therapeutic effect.

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