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

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Abstract

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.

Section snippets

Methods

Stained and unstained initial biopsy slides of previously diagnosed and treated large IMTs were acquired without identifiers from members of the Surgical Discipline Committee of the Children's Oncology Group who were associated with 5 clinical centers.1

Results

Eighteen samples were reviewed (Table 1). Eleven met all histological criteria for the diagnosis of IMT, 6 cases were considered consistent with IMT, and 1 case had hypercellularity, atypia, abundant ganglionlike cells, and a round cell transformation consistent with malignant transformation of IMT. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tissue for ALK-1 in 17 of 18 cases. Six (35%) of 17 cases displayed reactivity for ALK-1 (Fig. 1), all of which showed a

Discussion

Composed of organized vascular inflammatory tissue and myofibroblasts, IMTs often attain large size, invade normal tissues, and obstruct hollow organs. A component of the larger inflammatory pseudotumor histological grouping, they can occur in almost any part of the body and most frequently obstruct ureters, bowel, bile ducts, and bronchi [5], [6], [7]. Traditional treatment consists of attempts at radical surgical extirpation that often entails resection of involved or adjacent organs and

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    Presented at the 56th Annual Meeting of the Section on Surgery of the American Academy of Pediatrics, San Francisco, California, October 8-10, 2004.

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