The β5/focal adhesion kinase/glycogen synthase kinase 3β integrin pathway in high-grade osteosarcoma: a protein expression profile predictive of response to neoadjuvant chemotherapy
| Autor: | Jérôme Sales de Gauzy, Marie-Bernadette Delisle, Marie-Pierre Castex, Christine Chevreau, Elizabeth Cohen-Jonathan Moyal, A. Gomez-Brouchet, Sophie Le Guellec, Paul Bonnevialle, Hervé Rubie, Thomas Filleron |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Integrin beta Chains Adolescent Biopsy medicine.medical_treatment Bone Neoplasms Pathology and Forensic Medicine Metastasis Focal adhesion Glycogen Synthase Kinase 3 Young Adult Ezrin GSK-3 Biomarkers Tumor Humans Medicine Child Osteosarcoma Chemotherapy Glycogen Synthase Kinase 3 beta business.industry Kinase Middle Aged medicine.disease Chemotherapy regimen Neoadjuvant Therapy Focal Adhesion Kinase 2 Treatment Outcome Chemotherapy Adjuvant Tissue Array Analysis Cancer research Female business |
| Zdroj: | Human Pathology. 44:2149-2158 |
| ISSN: | 0046-8177 |
| DOI: | 10.1016/j.humpath.2013.03.020 |
| Popis: | To date, chemosensitivity to neoadjuvant chemotherapy of patients with high-grade osteosarcoma is evaluated on surgical resection by evaluation of the percentage of necrotic cells. As yet, no predictive profile of response to chemotherapy has been used in clinical practice. Because we have previously shown that the integrin pathway controls genotoxic-induced cell death and hypoxia, we hypothesized that in primary biopsies, expression of proteins involved in this pathway could be associated with sensitivity to neoadjuvant chemotherapy in high-grade osteosarcoma. We studied β1, β3, and β5 integrin expression and integrin-linked kinase, focal adhesion kinase (FAK), glycogen synthase kinase 3β (GSK3β), Rho B, angiopoietin-2, β-catenin, and ezrin expression by immunohistochemistry in 36 biopsies of osteosarcomas obtained before treatment. All patients received a chemotherapy regimen in the neoadjuvant setting. An immunoreactive score was assessed, combining the percentage of positive tumor cells and staining intensity. We evaluated the correlation of the biomarkers with response to chemotherapy, metastasis-free survival, and overall survival. A combination of 3 biomarkers (β5 integrin, FAK, and GSK3β) discriminated good and poor responders to chemotherapy, with the highest area under the curve (89.9%; 95% confidence interval, 77.4-1.00) and a diagnostic accuracy of 90.3%. Moreover, high expression of ezrin was associated with an increased risk of metastasis (hazard ratio, 3.93; 95% confidence interval, 1.19-12.9; P = .024). We report a protein expression profile in high-grade osteosarcoma associating β5 integrin, FAK, and GSK3β that significantly correlates with poor response to neoadjuvant chemotherapy. This biomarker profile could help select patients for whom an alternative protocol using inhibitors of this pathway can be proposed. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect