CTNNB1 S45F mutation predicts poor efficacy of meloxicam treatment for desmoid tumors: a pilot study.
CTNNB1 S45F mutation predicts poor efficacy of meloxicam treatment for desmoid tumors: a pilot study.
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DOI：
10.1371/journal.pone.0096391
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Nishida Y
中科院分区：
文献类型：
--
作者：
Hamada S;Futamura N;Ikuta K;Urakawa H;Kozawa E;Ishiguro N;Nishida Y
我们假设 CTNNB1（β-连环蛋白）突变模式会影响硬纤维瘤患者保守治疗的结果。本研究旨在确定 CTNNB1（β-连环蛋白）突变在预测接受美洛昔康（一种环加氧酶 2 (COX-2) 选择性抑制剂）治疗的硬纤维瘤患者治疗结果中的意义。 2003年至2012年间，连续33名腹膜外散发性硬纤维瘤患者前瞻性地使用美洛昔康作为初始全身药物治疗。美洛昔康的疗效根据实体瘤疗效评估标准（RECIST）进行评估。 DNA 是从冷冻组织或福尔马林固定材料中分离出来的。 CTNNB1突变分析通过直接测序进行。将免疫组织化学检测的核 β-catenin 染色阳性与 CTNNB1 突变状态进行比较。分析了美洛昔康治疗效果与 CTNNB1 突变状态之间的相关性。在接受美洛昔康治疗的 33 名患者中，1 名患者显示完全缓解（CR），7 名患者部分缓解（PR），12 名患者病情稳定（SD），13 名患者病情进展（PD）。 33例中有21例（64%）发现以下3种点突变：T41A（16例）、S45F（4例）和S45P（1例）。 β-catenin 的核表达与 CTNNB1 突变状态显着相关（p = 0.035）；所有 4 例 S45F 突变病例均表现出 β-catenin 的强核表达。 S45F 突变与不良反应显着相关（所有病例；PD）（p = 0.017），而其他突变对疗效没有影响。 CTNNB1 突变状态对于散发性硬纤维瘤患者的美洛昔康治疗具有重要的预后价值。
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.
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影响因子：
45.3
作者：
Ballo, MT;Zagars, GK;Pollock, RA
通讯作者：
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影响因子：
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