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Objective: To demonstrate that desmoid tumors (DTs) arise from mesenchymal stromal cells (MSCs) with mutations that deregulate Wnt signaling in a wound healing context.
Design: Human DTs were obtained from surgical specimens resected from patients under a protocol approved by the Institutional Review Board at the Brigham and Women’s Hospital (BWH). We examined expression of stem cell markers (CD73, CD90, Bmi-1) from 16 different specimens by immunohistochemistry (IHC) and fluorescent immunocytochemistry (IF). A DT-derived cell line from a patient with familial adenomatous polyposis (FAP) was also established and interrogated for MSC markers and tri-lineage potential. Finally, cells were evaluated for expression of full length versus truncated APC product.
Setting: Tertiary referral hospital
Patients: 16 BWH patients with DTs
Interventions: Not Applicable
Main Outcome Measures: Not Applicable
Results: All specimens contained cells expressing stem cell markers CD73, CD90, and Bmi-1, with co-expression of these markers in the same tumor cells. A DT-derived cell line showed expression of positive MSC markers (CD73, CD90, CD105) but not CD34, a negative marker, by IF and FACS analysis. Upon growth in differentiation media, we confirmed the ability of these DT-derived cells to differentiate into chondrocytes, osteocytes, and adipocytes. Cytochemistry for the C- vs. N-termini of APC confirmed that only truncated APC product was expressed in this DT-derived cell line.
Conclusion: This study supports the view that DT etiology involves the persistence of MSCs with deregulated Wnt signaling. The differentiation potential of these cells combined with expression of Bmi-1, a transcriptional repressor downstream of Hedgehog and Notch signaling, suggest that inhibitors targeting these pathways may provide a rational systemic therapy to prevent primary or recurrent DTs in high-risk patients.