The rationale for nonsteroidal anti-inflammatory drug therapy for inflammatory myofibroblastic tumors: a Children's Oncology Group study.
BACKGROUND
Inflammatory 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.


METHODS
The 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.


RESULTS
COX-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.


CONCLUSIONS
Our data suggest that the mediators of angiogenesis, VEGF and COX-2, are present and may play an important role in the growth of IMTs.
Division of Pediatric Surgery, Kaiser Permanente Medical Center, Los Angeles, CA 90027, USA. harry.applebaum@kp.org
Harry
H
Applebaum
Mark W
MW
Kieran
Timothy P
TP
Cripe
Cheryl M
CM
Coffin
Margaret H
MH
Collins
Arja
A
Kaipainen
Andrea
A
Laforme
Robert C
RC
Shamberger
D030301:Activin Receptors, Type II; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009379:Neoplasms, Muscle Tissue / Q000188:drug therapy / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism; D012189:Retrospective Studies; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008565:Membrane Proteins; D042442:Vascular Endothelial Growth Factors; D051546:Cyclooxygenase 2; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II