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The rationale for nonsteroidal anti-inflammatory drug therapy for inflammatory myofibroblastic tumors: a Children's Oncology Group study |
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| Authors: | Applebaum Harry Kieran Mark W Cripe Timothy P Coffin Cheryl M Collins Margaret H Kaipainen Arja Laforme Andrea Shamberger Robert C |
| Institution: | a Division of Pediatric Surgery, Kaiser Permanente Medical Center, Los Angeles, CA 90027, USA b Department of Pediatric Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA c Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA d Department of Pathology, University of Utah and Primary Children's Medical Center, Salt Lake City, UT, USA e Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH 84113, USA f Department of Vascular Biology, Children's Hospital Boston, MA 02115, USA g Department of Surgery, Children's Hospital Boston, MA 02115, USA |
| Abstract: | BackgroundInflammatory myofibroblastic tumors (IMTs) are neoplasms that are highly vascularized, have an intermediate prognosis, and are associated with infiltration, obstruction, local recurrence, and rare metastasis. Resection of large IMTs can lead to substantial morbidity and even mortality. Anecdotal experience suggests that nonsteroidal anti-inflammatory drugs may eradicate large IMTs or shrink them to a more readily resectable size and configuration. To support the hypothesis that nonsteroidal anti-inflammatory drugs are antiangiogenic for IMTs by interfering with vascular endothelial growth factor (VEGF) signaling via cyclooxygenase 2 (COX-2) inhibition, IMT specimens were immunohistochemically examined for expression of COX-2 enzyme and VEGF.MethodsThe diagnosis of IMT was confirmed in all 18 cases comprising the study. Intensity of COX-2 and VEGF staining was graded, and staining uniformity was examined. ALK-1 protein expression, found in up to two thirds of IMTs, was also determined.ResultsCOX-2 and VEGF expression were identified in all tissue examined, with staining intensity varying independently. ALK-1 protein expression was identified in 33% of specimens. Its presence was not related to the intensity of COX-2 or VEGF staining.ConclusionsOur data suggest that the mediators of angiogenesis, VEGF and COX-2, are present and may play an important role in the growth of IMTs. |
| Keywords: | Inflammatory myofibroblastic tumor (IMT) Nonsteroidal anti-inflammatory drug (NSAID) ALK-1 gene Vascular endothelial growth factor (VEGF) Cyclooxygenase 2 (COX-2) |
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