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Protein expression of KIT and gene mutation of c-kit and PDGFRs in Ewing sarcomas.
Pathol Res Pract. 2007; 203(3):127-34.PR

Abstract

Ewing sarcoma is a highly malignant tumor of bone preferentially arising in children and young adults. Its 5-year survival rate is only 50% despite the use of multimodal therapeutic approaches, requiring a search for new therapeutic targets and the development of novel therapeutic modalities. KIT and PDGFRs are type III receptor tyrosine kinases, and activating mutations in c-kit (which encodes KIT) and PDGFRs have been reported as oncogenic events in many malignancies. Imatinib is a selective inhibitor of KIT, PDGFR, and ABL tyrosine kinase activity and exerts different anti-tumor effects according to the regions of mutations in c-kit and PDGFR genes. Thus, we evaluated the immunohistochemical expression of KIT protein and the mutational status of exons 9, 11, 13, and 17 of the c-kit gene, exons 12 and 18 of the PDGFRA gene, and exon 12 of the PDGFRB gene in 71 formalin-fixed, paraffin-embedded Ewing sarcomas to increase our understanding of the potential, if any, of imatinib treatment for this malignancy. Of the 71 samples, 27 (38%) were immunohistochemically positive for KIT; however, activating mutations in c-kit were found in only 2 of 71 Ewing sarcomas (2.6%) within exon 9. No activating mutations in the PDGFRA and PDGFRB genes were found, but pleomorphism was identified in exon 18 of the PDGFRA gene. Our results for KIT protein expression agree with those of previous studies. This is the largest series of c-kit mutational analysis in Ewing sarcoma to date, and the results definitively show that c-kit activating mutations are not coincident with KIT protein expression in Ewing sarcoma in most samples. These findings imply other mechanisms for KIT activity and leave open the question of whether imatinib would be efficacious in the treatment of Ewing sarcoma.

Authors+Show Affiliations

Department of Pathology, Kyung Hee University Hospital, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-702, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17298867

Citation

Do, Ingu, et al. "Protein Expression of KIT and Gene Mutation of C-kit and PDGFRs in Ewing Sarcomas." Pathology, Research and Practice, vol. 203, no. 3, 2007, pp. 127-34.
Do I, Araujo ES, Kalil RK, et al. Protein expression of KIT and gene mutation of c-kit and PDGFRs in Ewing sarcomas. Pathol Res Pract. 2007;203(3):127-34.
Do, I., Araujo, E. S., Kalil, R. K., Bacchini, P., Bertoni, F., Unni, K. K., & Park, Y. K. (2007). Protein expression of KIT and gene mutation of c-kit and PDGFRs in Ewing sarcomas. Pathology, Research and Practice, 203(3), 127-34.
Do I, et al. Protein Expression of KIT and Gene Mutation of C-kit and PDGFRs in Ewing Sarcomas. Pathol Res Pract. 2007;203(3):127-34. PubMed PMID: 17298867.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protein expression of KIT and gene mutation of c-kit and PDGFRs in Ewing sarcomas. AU - Do,Ingu, AU - Araujo,Eduard Santini, AU - Kalil,Ricardo K, AU - Bacchini,Patrizia, AU - Bertoni,Franco, AU - Unni,K Krishnan, AU - Park,Yong-Koo, Y1 - 2007/02/12/ PY - 2006/08/23/received PY - 2006/12/07/accepted PY - 2007/2/15/pubmed PY - 2007/5/5/medline PY - 2007/2/15/entrez SP - 127 EP - 34 JF - Pathology, research and practice JO - Pathol. Res. Pract. VL - 203 IS - 3 N2 - Ewing sarcoma is a highly malignant tumor of bone preferentially arising in children and young adults. Its 5-year survival rate is only 50% despite the use of multimodal therapeutic approaches, requiring a search for new therapeutic targets and the development of novel therapeutic modalities. KIT and PDGFRs are type III receptor tyrosine kinases, and activating mutations in c-kit (which encodes KIT) and PDGFRs have been reported as oncogenic events in many malignancies. Imatinib is a selective inhibitor of KIT, PDGFR, and ABL tyrosine kinase activity and exerts different anti-tumor effects according to the regions of mutations in c-kit and PDGFR genes. Thus, we evaluated the immunohistochemical expression of KIT protein and the mutational status of exons 9, 11, 13, and 17 of the c-kit gene, exons 12 and 18 of the PDGFRA gene, and exon 12 of the PDGFRB gene in 71 formalin-fixed, paraffin-embedded Ewing sarcomas to increase our understanding of the potential, if any, of imatinib treatment for this malignancy. Of the 71 samples, 27 (38%) were immunohistochemically positive for KIT; however, activating mutations in c-kit were found in only 2 of 71 Ewing sarcomas (2.6%) within exon 9. No activating mutations in the PDGFRA and PDGFRB genes were found, but pleomorphism was identified in exon 18 of the PDGFRA gene. Our results for KIT protein expression agree with those of previous studies. This is the largest series of c-kit mutational analysis in Ewing sarcoma to date, and the results definitively show that c-kit activating mutations are not coincident with KIT protein expression in Ewing sarcoma in most samples. These findings imply other mechanisms for KIT activity and leave open the question of whether imatinib would be efficacious in the treatment of Ewing sarcoma. SN - 0344-0338 UR - https://www.unboundmedicine.com/medline/citation/17298867/Protein_expression_of_KIT_and_gene_mutation_of_c_kit_and_PDGFRs_in_Ewing_sarcomas_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0344-0338(07)00006-4 DB - PRIME DP - Unbound Medicine ER -