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Molecular Cancer Therapeutics
Molecular Cancer Therapeutics

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Companion Diagnostics and Cancer Biomarkers

MRP1 Overexpression Determines Poor Prognosis in Prospectively Treated Patients with Localized High-Risk Soft Tissue Sarcoma of Limbs and Trunk Wall: An ISG/GEIS Study

Javier Martin-Broto, Antonio M. Gutierrez, Rafael F. Ramos, José A. Lopez-Guerrero, Stefano Ferrari, Silvia Stacchiotti, Piero Picci, Silvia Calabuig, Paola Collini, Marco Gambarotti, Silvia Bague, Angelo P. Dei Tos, Elena Palassini, Pablo Luna, Josefina Cruz, Ricardo Cubedo, Javier Martinez-Trufero, Andres Poveda, Paolo G. Casali, Antonio Fernandez-Serra, Antonio Lopez-Pousa and Alessandro Gronchi
Javier Martin-Broto
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Antonio M. Gutierrez
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Rafael F. Ramos
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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José A. Lopez-Guerrero
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Stefano Ferrari
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Silvia Stacchiotti
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Piero Picci
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Silvia Calabuig
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Paola Collini
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Marco Gambarotti
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Silvia Bague
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Angelo P. Dei Tos
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Elena Palassini
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Pablo Luna
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Josefina Cruz
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Ricardo Cubedo
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Javier Martinez-Trufero
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Andres Poveda
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Paolo G. Casali
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Antonio Fernandez-Serra
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Antonio Lopez-Pousa
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Alessandro Gronchi
Authors' Affiliations: Department of Oncology, Clinical and Translational Cancer Research Group, Department of Pathology, University Hospital Son Espases, Palma de Mallorca, Spain; Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain; Chemotherapy Department, Istituto Ortopedico Rizzoli, Bologna, Italy; Adult Mesenchymal Tumor, Medical Oncology Unit, Cancer Med Dpt; 2nd Division of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Pathology, Hospital Sant Pau, Barcelona, Spain; Anatomic Pathology, Department of Oncology, General Hospital of Treviso, Treviso, Italy; Department of Oncology, University Hospital of Canarias, La Laguna, Spain; Department of Oncology, Hospital Puerta de Hierro, Madrid, Spain; Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain; Department of Oncology, Fundación IVO. Valencia, Spain; Department of Oncology, Hospital Sant Pau, Barcelona, Spain; Department of Surgery, Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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DOI: 10.1158/1535-7163.MCT-13-0406 Published January 2014
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Abstract

Patients with localized high-risk soft tissue sarcomas (STS) of the limbs and trunk wall still have a considerable metastatic recurrence rate of more than 50%, in spite of adjuvant chemotherapy. This drug-ceiling effect of chemotherapy in sarcoma setting could be explained, at least partially, by multidrug resistance (MDR) mechanisms. The aim of this study was to ascertain whether mRNA and protein expression of ABCB1 (P-glycoprotein), ABCC1 (MRP1), and GSTA1 (glutathione S-transferase pi) was prognostic in localized high-risk STS. Immunohistochemistry and reverse transcriptase-PCR studies were performed from biopsies at the time of diagnosis. Patients of this series were prospectively enrolled into a phase III trial that compared three versus five cycles of epirubicin plus ifosfamide. The series of 102 patients found 41 events of recurrence and 37 of death with a median follow-up of 68 months. In univariate analysis, variables with a statistically significant relationship with relapse-free survival (RFS) were: MRP1 expression (5-year RFS rate of 23% in positive cases and 63% in negative cases, P = 0.029), histology (5-year RFS rate of 74% in undifferentiated pleomorphic sarcoma and 43% in synovial sarcoma, P = 0.028), and ABCC1 expression (5-year RFS rate of 33% in overexpression and 65% in downregulation, P = 0.012). Combined ABCC1/MRP1 was the only independent prognostic factor for both RFS (HR = 2.704, P = 0.005) and overall survival (HR = 2.208, P = 0.029). ABCC1/MRP1 expression shows robust prognostic relevance in patients with localized high-risk STS treated with anthracycline-based chemotherapy, which is the standard front line treatment in STS. This finding deserves attention as it points to a new targetable protein in STS. Mol Cancer Ther; 13(1); 249–59. ©2013 AACR.

  • Received May 29, 2013.
  • Revision received September 23, 2013.
  • Accepted October 15, 2013.
  • ©2013 American Association for Cancer Research.
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Molecular Cancer Therapeutics: 13 (1)
January 2014
Volume 13, Issue 1
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MRP1 Overexpression Determines Poor Prognosis in Prospectively Treated Patients with Localized High-Risk Soft Tissue Sarcoma of Limbs and Trunk Wall: An ISG/GEIS Study
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MRP1 Overexpression Determines Poor Prognosis in Prospectively Treated Patients with Localized High-Risk Soft Tissue Sarcoma of Limbs and Trunk Wall: An ISG/GEIS Study
Javier Martin-Broto, Antonio M. Gutierrez, Rafael F. Ramos, José A. Lopez-Guerrero, Stefano Ferrari, Silvia Stacchiotti, Piero Picci, Silvia Calabuig, Paola Collini, Marco Gambarotti, Silvia Bague, Angelo P. Dei Tos, Elena Palassini, Pablo Luna, Josefina Cruz, Ricardo Cubedo, Javier Martinez-Trufero, Andres Poveda, Paolo G. Casali, Antonio Fernandez-Serra, Antonio Lopez-Pousa and Alessandro Gronchi
Mol Cancer Ther January 1 2014 (13) (1) 249-259; DOI: 10.1158/1535-7163.MCT-13-0406

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MRP1 Overexpression Determines Poor Prognosis in Prospectively Treated Patients with Localized High-Risk Soft Tissue Sarcoma of Limbs and Trunk Wall: An ISG/GEIS Study
Javier Martin-Broto, Antonio M. Gutierrez, Rafael F. Ramos, José A. Lopez-Guerrero, Stefano Ferrari, Silvia Stacchiotti, Piero Picci, Silvia Calabuig, Paola Collini, Marco Gambarotti, Silvia Bague, Angelo P. Dei Tos, Elena Palassini, Pablo Luna, Josefina Cruz, Ricardo Cubedo, Javier Martinez-Trufero, Andres Poveda, Paolo G. Casali, Antonio Fernandez-Serra, Antonio Lopez-Pousa and Alessandro Gronchi
Mol Cancer Ther January 1 2014 (13) (1) 249-259; DOI: 10.1158/1535-7163.MCT-13-0406
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Molecular Cancer Therapeutics
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