CTNNB1 S45F mutation predicts poor efficacy of meloxicam treatment for desmoid tumors: a pilot study.

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.

• Authors: Shunsuke Hamada, Naohisa Futamura, Kunihiro Ikuta, Hiroshi Urakawa, Eiji Kozawa, Naoki Ishiguro, Yoshihiro Nishida
• Journal: PloS one (PLoS One) Vol. 9 Issue 5 Pg. e96391 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24788118 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• CTNNB1 protein, human
• Thiazines
• Thiazoles
• beta Catenin
• Meloxicam

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Cell Nucleus (metabolism)
• Child
• Female
• Fibromatosis, Abdominal (drug therapy, genetics)
• Fibromatosis, Aggressive (drug therapy, genetics)
• Humans
• Male
• Meloxicam
• Middle Aged
• Pilot Projects
• Point Mutation
• Retrospective Studies
• Thiazines (therapeutic use)
• Thiazoles (therapeutic use)
• Treatment Outcome
• Young Adult
• beta Catenin (genetics, metabolism)