Nuclear expression of β-catenin predicts the efficacy of meloxicam treatment for patients with sporadic desmoid tumors

Hamada, Shunsuke; Urakawa, Hiroshi; Kozawa, Eiji; Futamura, Naohisa; Ikuta, Kazunari; Shimoyama, Yoshie; Nakamura, Shigeo; Ishiguro, Naoki; Nishida, Yoshihiro

doi:10.1007/s13277-013-1600-7

Cited by 13 publications

(22 citation statements)

References 30 publications

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“…Meloxicam treatment for patients with extraperitoneal desmoid tumors was approved by the Institutional Review Board of the Center for Advanced Medicine and Clinical Research of Nagoya University (Nagoya, Japan). Favorable short-term results were initially reported (14,17); however, several patients subsequently exhibited resistance to meloxicam treatment (18). Since 2009, the treatment modality was formally organized with low-dose chemotherapy (methotrexate and vinblastine) or planned simple surgery for patients with desmoid tumors refractory to or stable to meloxicam treatment.…”

Section: Methodsmentioning

confidence: 99%

Simple resection of truncal desmoid tumors: A case series

et al. 2016

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Abstract. Desmoid tumors of the extra-abdominal and abdominal wall have been associated with morbidity due to the aggressive nature of the surgery and high recurrence rates. Surgery that does not cause functional impairment is desired for patients with desmoid tumors. In the present study, among patients with desmoid tumors who were prospectively and consecutively treated with identical conservative treatment with meloxicam, a selected patients of patients were treated with less invasive surgery than wide-resection. Out of 60 patients pathologically diagnosed with desmoid tumors, 9 patients with tumors refractory to conservative treatment and 4 patients who refused to receive this type of treatment were treated with planned simple resection. Subsequently, the clinical outcome of the patients and the mutational status of the catenin β-1 (CTNNB1) gene in the tumors were analyzed. The mean age of the 13 patients that underwent planned simple resection was 39 years, and the tumors were located in the abdominal wall in 6 cases, the chest wall in 4 cases and the neck in 3 cases. All excised specimens were evaluated and positive microscopic margins were identified; however, during the mean follow-up period of 30 months, 12/13 cases, 7 of which had T41A mutations and 5 of which had no mutations (wild-type), did not develop recurrence. Only 1 initial case with an S45F mutation in the CTNNB1 gene developed recurrence. The results of the present prospectively treated with simple resection and retrospectively analyzed study suggest that planned simple resection could serve as a therapeutic modality for extraperitoneal desmoid tumors, particularly truncal ones with a wild-type or T41A mutational status.

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Section: Methodsmentioning

confidence: 99%

Simple resection of truncal desmoid tumors: A case series

et al. 2016

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“…DF has also been reported to occur at sites of previous surgery or blunt trauma [2,11,12]. Sporadic cases show a mutation in the β-catenin gene on 3p21, resulting in overexpression of β-catenin in the nucleus [13,14]. 14β-catenin plays an important role in regulating the size of skin wounds and mediates the action of TGF-β, which is known to promote wound hyperplasia through proliferation of fibroblasts [13,14].…”

Section: Introductionmentioning

confidence: 99%

“…Sporadic cases show a mutation in the β-catenin gene on 3p21, resulting in overexpression of β-catenin in the nucleus [13,14]. 14β-catenin plays an important role in regulating the size of skin wounds and mediates the action of TGF-β, which is known to promote wound hyperplasia through proliferation of fibroblasts [13,14]. Thus, it can be assumed that DF represents partially uncontrolled wound healing [2].…”

Section: Introductionmentioning

confidence: 99%

“…Approximately 80% of neoplasms show granular nuclear expression of β-catenin [13,14]. Histologic differential diagnosis is broad and encompasses a wide range of spindle cell lesions, ranging from scarring to abdominal gastrointestinal stromal tumors and liposarcoma with 'low grade' dedifferentiation [15,16].…”

Section: Introductionmentioning

confidence: 99%

“…Histologic differential diagnosis is broad and encompasses a wide range of spindle cell lesions, ranging from scarring to abdominal gastrointestinal stromal tumors and liposarcoma with 'low grade' dedifferentiation [15,16]. However, most neoplasms resembling fibroma have specific histological diagnostic characteristics and can be confidently diagnosed by the absence of nuclear β-catenin immunoreactivity [13,14].…”

Section: Introductionmentioning

confidence: 99%

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Possible involvement of cyclooxygenase-2 in the recurrence of desmoid fibromatosis: case series and mini-review of the literature

Hashimoto¹,

Nishimura²,

Oka³

et al. 2018

biomedicalresearch

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Background: Desmoid fibromatosis (DF) is a type of fibrous tumor that rarely metastasizes but often recurs locally. Cyclooxygenase-2 (COX-2) has been shown to be expressed in DF lesions, although its involvement in DF recurrence is unknown. We investigated the association between COX-2 expression and DF recurrence using immunohistochemistry. Patients and methods: Cases of DF treated in our hospital between March 2000 and December 2012 were reviewed. We used immunohistochemistry to identify COX-2 expression in resected specimens from these cases. The relationship between recurrence and age, sex, duration of disease, size of tumor, tumor site, spontaneous pain, inflammation, and COX-2 expression was studied. Results: In the ten included cases (mean age, 55.2 y; 5 male and 5 female patients), we found that COX-2 expression was significantly associated with DF recurrence (p=0.01). Conclusion: Our findings indicate that COX-2 is involved in recurrence of DF.

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Characteristics of cultured desmoid cells with different CTNNB1 mutation status

et al. 2015

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Desmoid tumors are benign mesenchymal neoplasms with a locally aggressive nature. The mutational status of β‐catenin gene (CTNNB1) is presumed to affect the tumorous activity of the cells. In this study, we isolated three kinds of desmoid cell with different CTNNB1 status, and compared their characteristics. Cells were isolated from three patients with abdominal wall desmoid during surgery, all of which were resistant to meloxicam treatment. The mutational status of the CTNNB1 exon 3 was determined for both parental tumor tissues and isolated cultured cells. β‐catenin expression was determined with immunohistochemistry. Responsiveness to meloxicam was investigated with MTS assay together with COX‐2 immunostaining. mRNA expressions of downstream molecules of Wnt/β‐catenin pathway were determined with real‐time RT‐PCR. Three kinds of cell isolated from desmoid tumors harboring different CTNNB1 mutation status (wild type, T41A, and S45F), all exhibited a spindle shape. These isolated cells could be cultured until the 20th passage with unchanged proliferative activity. Nuclear accumulation of β‐catenin was observed in all cultured cells, particularly in those with S45F. Proliferating activity was significantly suppressed by meloxicam (25 μmol/L, P < 0.007) in all three cell cultures, of which parental desmoid was resistant to meloxicam clinically. The mRNA expressions of Axin2, c‐Myc, and Cyclin D1 differently increased in the three cultured cell types as compared with those in human skin fibroblast cells (HDF). Inhibitors of Wnt/β‐catenin pathway downregulated Axin2, c‐Myc, and Cyclin D1 significantly. Isolated and cultured desmoid tumor cells harboring any one of the CTNNB1 mutation status had unique characteristics, and could be useful to investigate desmoid tumors with different mutation status of CTNNB1.

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Nuclear expression of β-catenin predicts the efficacy of meloxicam treatment for patients with sporadic desmoid tumors

Cited by 13 publications

References 30 publications

Simple resection of truncal desmoid tumors: A case series

Simple resection of truncal desmoid tumors: A case series

Possible involvement of cyclooxygenase-2 in the recurrence of desmoid fibromatosis: case series and mini-review of the literature

Characteristics of cultured desmoid cells with different CTNNB1 mutation status

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