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- W2596780106 abstract "10076 Background: Up to now, chemosensitivity to neoadjuvant chemotherapy performed for patients with osteosarcoma is evaluated on the surgical resection by the evaluation of the percentage of necrotic cells. No predictive profile of chemotherapy has been described yet. Because we have previously shown that integrin pathway controls genotoxic-induced cell death and hypoxia via ILK, FAK and RhoB, we hypothesized that the expression of the proteins involved in this pathway in pre-treatment biopsies could be associated with sensitivity to chemotherapy in osteosarcoma. Methods: We studied by immunohistochemistry β1, β3, β5, integrins, ILK, FAK, GSK-3β, RhoB and Ang-2 expression in 36 osteosarcomas biopsies of patients obtained before treatment. All the patients were treated by the SFOP OS94 chemotherapy protocol and underwent wide conservative surgery. Response to preoperative chemotherapy was assessed on the surgical resection by the Rosen’s protocol. An immunoreactive score (IRS) was assessed, combining the percentage of positive tumour cells and staining intensity. We evaluated the correlation of the selected markers expression with response to preoperative chemotherapy and clinical outcome. Results: FAK expression was statistically linked with ILK expression (rho=0.43; p=0.020), β1integrin expression with FAK expression (rho=0.51); p=0.003), RhoB with ILK expression (rho=0.55; p=0.002), and β1 with β3integrin expression (rho=0.70; p<.001), suggesting that a regulation of the integrin pathway that we studied might exist in high grade osteosarcoma. Moreover, the combination of β5 integrin, FAK and GSK-3β discriminated good and poor responder to chemotherapy (89.9%; 95% CI= [77.4;1.00], yielding a sensitivity of 94.1%, a specificity of 85.7% and a diagnostic accuracy of 90.3%. Conclusions: We report for the first time a protein expression profile on pre-treatment biopsies associating β5 integrin FAK and GSK-3β related with a poor response to neoadjuvant chemotherapy. This profile could help to select patients for clinical trials using inhibitors of this pathway in association with chemotherapy." @default.
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- W2596780106 date "2012-05-20" @default.
- W2596780106 modified "2023-10-16" @default.
- W2596780106 title "Study of the expression of integrin pathway's proteins as predictive markers of response to neoadjuvant chemotherapy in pretreatment biopsies of patients with high-grade osteosarcoma." @default.
- W2596780106 doi "https://doi.org/10.1200/jco.2012.30.15_suppl.10076" @default.
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