TAILIEUCHUNG - Báo cáo y học: "Frequent activation of EGFR in advanced chordomas"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Critical Care giúp cho các bạn có thêm kiến thức về ngành y học đề tài: Frequent activation of EGFR in advanced chordomas. | Dewaele et al. Clinical Sarcoma Research 2011 1 4 http content 1 1 4 CLINICAL SARCOMA RESEARCH RESEARCH Open Access Frequent activation of EGFR in advanced chordomas 1 2 3 4 1 Barbara Dewaele Francesca Maggiani Giuseppe Floris Michèle Ampe Vanessa Vanspauwen Agnieszka Wozniak3 Maria Debiec-Rychter1 and Raf Sciot2 Abstract Background Chordomas are rare neoplasms arising from notochordal remnants in the midline skeletal axis for which the current treatment is limited to surgery and radiotherapy. Recent reports suggest that receptor tyrosine kinases RTK might be essential for the survival or proliferation of chordoma cells providing a rationale for RTK targeted therapy. Nevertheless the reported data are conflicting most likely due to the assorted tumor specimens used for the studies and the heterogeneous methodological approaches. In the present study we performed a comprehensive characterization of this rare entity using a wide range of assays in search for relevant therapeutic targets. Methods Histopathological features of 42 chordoma specimens 21 primary and 21 advanced were assessed by immunohistochemistry and fluorescent in situ hybridization FISH using PDGFRB CSF1R and EGFR probes. Twenty-two of these cases for which frozen material was available nine primary and 13 advanced tumors were selectively analyzed using the whole-genome K TK-CGH-array phospho-kinase antibody array or Western immunoblotting. The study was supplemented by direct sequencing of KIT PDGFRB CSF1R and EGFR. Results We demonstrated that EGFR is frequently and the most significantly activated RTK in chordomas. Furthermore concurrent to EGFR activation the tumors commonly reveal co-activation of alternative RTK. The consistent activation of AKT the frequent loss of the tumor suppressor PTEN allele the recurrent activation of upstream RTK and of downstream effectors like p70S6K and mTOR all indicate the PI3K AKT pathway as an important mediator of .

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