PURPOSE: Multiple drug resistance due to P-glycoprotein (P-gp) expression has been reported to be a cause of disease recurrence in osteosarcoma. Tumor specimens derived from children and young adults with osteosarcoma enrolled onto a national Intergroup trial (INT0133) were analyzed prospectively to determine the role of multiple drug resistance in osteosarcoma. PATIENTS AND METHODS: From October 15, 1992, to November 25, 1997, 685 patients with localized, high-grade osteosarcoma were enrolled onto INT0133. Paraffin-embedded diagnostic tumor specimens were assayed for P-gp using monoclonal antibodies C-494 (139 patients) and JSB-1 (133 patients). Percent necrosis at the time of definitive surgery (NEC), event-free survival (EFS), and overall survival (OS) were evaluated as outcome measures for patients with P-gp-positive disease and were compared with patients with P-gp-negative disease. RESULTS: P-gp expression in the biopsy specimen did not significantly increase the risk for adverse outcomes as measured by EFS, OS, or NEC. EFS for those patients with C-494-positive tumors was 59% at 4 years versus 61% at 4 years for patients with C-494-negative tumors (P = .79), or 58% at 4 years versus 61% at 4 years for patients with JSB-1-positive versus JSB-1-negative tumors (P = .65). OS for patients with C-494-positive tumors was 82% at 4 years versus 82% at 4 years for patients with C-494-negative tumors (P = .61). CONCLUSION: Prospective analysis of the role of multiple drug resistance in localized osteosarcoma did not find that immunohistochemical analysis of P-gp expression predicted outcome for patients treated on INT0133.
PURPOSE: Multiple drug resistance due to P-glycoprotein (P-gp) expression has been reported to be a cause of disease recurrence in osteosarcoma. Tumor specimens derived from children and young adults with osteosarcoma enrolled onto a national Intergroup trial (INT0133) were analyzed prospectively to determine the role of multiple drug resistance in osteosarcoma. PATIENTS AND METHODS: From October 15, 1992, to November 25, 1997, 685 patients with localized, high-grade osteosarcoma were enrolled onto INT0133. Paraffin-embedded diagnostic tumor specimens were assayed for P-gp using monoclonal antibodies C-494 (139 patients) and JSB-1 (133 patients). Percent necrosis at the time of definitive surgery (NEC), event-free survival (EFS), and overall survival (OS) were evaluated as outcome measures for patients with P-gp-positive disease and were compared with patients with P-gp-negative disease. RESULTS:P-gp expression in the biopsy specimen did not significantly increase the risk for adverse outcomes as measured by EFS, OS, or NEC. EFS for those patients with C-494-positive tumors was 59% at 4 years versus 61% at 4 years for patients with C-494-negative tumors (P = .79), or 58% at 4 years versus 61% at 4 years for patients with JSB-1-positive versus JSB-1-negative tumors (P = .65). OS for patients with C-494-positive tumors was 82% at 4 years versus 82% at 4 years for patients with C-494-negative tumors (P = .61). CONCLUSION: Prospective analysis of the role of multiple drug resistance in localized osteosarcoma did not find that immunohistochemical analysis of P-gp expression predicted outcome for patients treated on INT0133.
Authors: Sarah Gorlick; Donald A Barkauskas; Mark Krailo; Sajida Piperdi; Rebecca Sowers; Jonathan Gill; David Geller; R Lor Randall; Katherine Janeway; Cindy Schwartz; Holcombe Grier; Paul A Meyers; Richard Gorlick; Mark Bernstein; Neyssa Marina Journal: Pediatr Blood Cancer Date: 2014-04-22 Impact factor: 3.167
Authors: David Delgado; Daniel E Webster; Kenneth B DeSantes; Emily T Durkin; Aimen F Shaaban Journal: Pediatr Blood Cancer Date: 2010-12-15 Impact factor: 3.167
Authors: Monrat Chulanetra; Atthapan Morchang; Elias Sayour; Lamis Eldjerou; Rowan Milner; Joanne Lagmay; Matt Cascio; Brian Stover; William Slayton; Wanpen Chaicumpa; Pa-Thai Yenchitsomanus; Lung-Ji Chang Journal: Am J Cancer Res Date: 2020-02-01 Impact factor: 6.166