Abstract
We hypothesized that patterns of CTNNB1 (β-catenin) mutations would affect the outcome of conservative therapy in patients with desmoid tumors. This study aimed to determine the significance of CTNNB1 (β-catenin) mutations in predicting the treatment outcome in patients with desmoid tumors treated with meloxicam, a cyclooxygenase-2 (COX-2) selective inhibitor. Between 2003 and 2012, consecutive thirty-three patients with extra-peritoneal sporadic desmoid tumors were prospectively treated with meloxicam as the initial systemic medical therapy. The efficacy of meloxicam was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). DNA was isolated from frozen tissue or formalin-fixed materials. CTNNB1 mutation analysis was performed by direct sequencing. Positivity of nuclear β-catenin staining by immunohistochemistry was compared with the status of CTNNB1 mutations. The correlation between the efficacy of meloxicam treatment and status of CTNNB1 mutations was analyzed. Of the 33 patients with meloxicam treatment, one showed complete remission (CR), 7 partial remission (PR), 12 stable disease (SD), and 13 progressive disease (PD). The following 3 point mutations were identified in 21 of the 33 cases (64%): T41A (16 cases), S45F (4 cases) and S45P (one case). The nuclear expression of β-catenin correlated significantly with CTNNB1 mutation status (p = 0.035); all four cases with S45F mutation exhibited strong nuclear expression of β-catenin. S45F mutation was significantly associated with a poor response (all cases; PD) (p = 0.017), whereas the other mutations had no impact on efficacy. The CTNNB1 mutation status was of significant prognostic value for meloxicam treatment in patients with sporadic desmoid tumors.
Highlights
Desmoid tumors, known as aggressive fibromatosis, are mesenchymal tumors that show marked local aggressiveness, but rarely metastasize, and do not cause disease-specific death if they are not located at anatomically critical sites [1], [2]
Clinical features and efficacy of meloxicam treatment Of the 33 patients prospectively treated with meloxicam, 11 were male, and 22 were female
The nuclear accumulation of b-catenin caused by CTNNB1 or APC mutation subsequently activates T-cell factor, which in turn causes transcription of target genes such as c-MYC and cyclin D [25], [26]
Summary
Known as aggressive fibromatosis, are mesenchymal tumors that show marked local aggressiveness, but rarely metastasize, and do not cause disease-specific death if they are not located at anatomically critical sites [1], [2]. Extraperitoneal desmoid tumors, which are usually sporadic in nature, occur across a wide age range, and can arise at virtually any body site. Radical surgical intervention and/or repeated surgery due to a high recurrence rate (range 34–53% at 5 years) [3], [4] occasionally lead to significant treatment-related morbidity including amputation or significant functional impairment. Several reports have failed to demonstrate the significance of margin status in surgery for local recurrence [3,4,5], while spontaneous regression has been reported [5], [6]. Several authors recently demonstrated the effectiveness of conservative treatment for desmoid tumors including radiotherapy and pharmacological treatment [7], [8]. The efficacy of these treatments cannot be predicted, and so remains a crucial problem
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
