Immunohistochemical staining with non-phospho β-catenin as a diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with extra-peritoneal desmoid-type fibromatosis
Abstract Background Immunohistochemical staining with conventional anti-β-catenin antibody has been applied as a diagnostic tool for desmoid-type fibromatosis (DF). This study aimed to evaluate the diagnostic and prognostic value of immunohistochemical staining with anti-non-phospho β-catenin antibo...
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| Format: | Article |
| Language: | English |
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BMC
2017-08-01
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| Series: | Diagnostic Pathology |
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| Online Access: | http://link.springer.com/article/10.1186/s13000-017-0654-z |
| _version_ | 1818926093671858176 |
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| author | Tomohisa Sakai Yoshihiro Nishida Shunsuke Hamada Hiroshi Koike Kunihiro Ikuta Takehiro Ota Naoki Ishiguro |
| author_facet | Tomohisa Sakai Yoshihiro Nishida Shunsuke Hamada Hiroshi Koike Kunihiro Ikuta Takehiro Ota Naoki Ishiguro |
| author_sort | Tomohisa Sakai |
| collection | DOAJ |
| description | Abstract Background Immunohistochemical staining with conventional anti-β-catenin antibody has been applied as a diagnostic tool for desmoid-type fibromatosis (DF). This study aimed to evaluate the diagnostic and prognostic value of immunohistochemical staining with anti-non-phospho β-catenin antibody, which might more accurately reflect the aggressiveness of DF, in comparison to the conventional anti-β-catenin antibody. Methods Between 2003 and 2015, 40 patients with extra-peritoneal sporadic DF were prospectively treated with meloxicam or celecoxib, a COX-2 inhibitor, therapy. The efficacy of this treatment was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). Immunohistochemical staining was performed on formalin-fixed material to evaluate the expression of β-catenin and non-phospho β-catenin, and the positivity was grouped as negative, weak, moderate, and strong. DNA was isolated from frozen tissue or formalin-fixed materials, and the CTNNB1 mutation status was determined by direct sequencing. Results Of the 40 patients receiving COX-2 inhibitor treatment, there was one with complete remission, 12 with partial remission, 7 with stable disease, and 20 with progressive disease. The mutation sites in CTNNB1 were detected in 22 (55%) of the 40 cases: T41A (17 cases), S45F (3 cases), and T41I and S45P (1 each). The positive nuclear expression of non-phospho β-catenin showed a significant correlation with positive CTNNB1 mutation status detected by Sanger method (p = 0.025), and poor outcome in COX-2 inhibitor therapy (p = 0.022). In contrast, nuclear expression of β-catenin did not show a significant correlation with either CTNNB1 mutation status (p = 0.43) or outcome of COX-2 inhibitor therapy (p = 0.38). Conclusions Nuclear expression of non-phospho β-catenin might more appropriately reflect the biological behavior of DF, and immunohistochemical staining with non-phospho β-catenin could serve as a more useful diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with DF. |
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| id | doaj.art-aecf0bb481c74bbd8b76e9623d6200bc |
| institution | Directory Open Access Journal |
| issn | 1746-1596 |
| language | English |
| last_indexed | 2024-12-20T02:51:38Z |
| publishDate | 2017-08-01 |
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| series | Diagnostic Pathology |
| spelling | doaj.art-aecf0bb481c74bbd8b76e9623d6200bc2022-12-21T19:56:01ZengBMCDiagnostic Pathology1746-15962017-08-011211910.1186/s13000-017-0654-zImmunohistochemical staining with non-phospho β-catenin as a diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with extra-peritoneal desmoid-type fibromatosisTomohisa Sakai0Yoshihiro Nishida1Shunsuke Hamada2Hiroshi Koike3Kunihiro Ikuta4Takehiro Ota5Naoki Ishiguro6Department of Orthopaedic Surgery, Nagoya University Graduate School and School of MedicineDepartment of Orthopaedic Surgery, Nagoya University Graduate School and School of MedicineDepartment of Orthopaedic Surgery, Nagoya University Graduate School and School of MedicineDepartment of Orthopaedic Surgery, Nagoya University Graduate School and School of MedicineDepartment of Orthopaedic Surgery, Nagoya University Graduate School and School of MedicineDepartment of Orthopaedic Surgery, Nagoya University Graduate School and School of MedicineDepartment of Orthopaedic Surgery, Nagoya University Graduate School and School of MedicineAbstract Background Immunohistochemical staining with conventional anti-β-catenin antibody has been applied as a diagnostic tool for desmoid-type fibromatosis (DF). This study aimed to evaluate the diagnostic and prognostic value of immunohistochemical staining with anti-non-phospho β-catenin antibody, which might more accurately reflect the aggressiveness of DF, in comparison to the conventional anti-β-catenin antibody. Methods Between 2003 and 2015, 40 patients with extra-peritoneal sporadic DF were prospectively treated with meloxicam or celecoxib, a COX-2 inhibitor, therapy. The efficacy of this treatment was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). Immunohistochemical staining was performed on formalin-fixed material to evaluate the expression of β-catenin and non-phospho β-catenin, and the positivity was grouped as negative, weak, moderate, and strong. DNA was isolated from frozen tissue or formalin-fixed materials, and the CTNNB1 mutation status was determined by direct sequencing. Results Of the 40 patients receiving COX-2 inhibitor treatment, there was one with complete remission, 12 with partial remission, 7 with stable disease, and 20 with progressive disease. The mutation sites in CTNNB1 were detected in 22 (55%) of the 40 cases: T41A (17 cases), S45F (3 cases), and T41I and S45P (1 each). The positive nuclear expression of non-phospho β-catenin showed a significant correlation with positive CTNNB1 mutation status detected by Sanger method (p = 0.025), and poor outcome in COX-2 inhibitor therapy (p = 0.022). In contrast, nuclear expression of β-catenin did not show a significant correlation with either CTNNB1 mutation status (p = 0.43) or outcome of COX-2 inhibitor therapy (p = 0.38). Conclusions Nuclear expression of non-phospho β-catenin might more appropriately reflect the biological behavior of DF, and immunohistochemical staining with non-phospho β-catenin could serve as a more useful diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with DF.http://link.springer.com/article/10.1186/s13000-017-0654-zNon-phospho β-cateninDesmoid-type fibromatosisMeloxicamPrognosisDiagnosis |
| spellingShingle | Tomohisa Sakai Yoshihiro Nishida Shunsuke Hamada Hiroshi Koike Kunihiro Ikuta Takehiro Ota Naoki Ishiguro Immunohistochemical staining with non-phospho β-catenin as a diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with extra-peritoneal desmoid-type fibromatosis Diagnostic Pathology Non-phospho β-catenin Desmoid-type fibromatosis Meloxicam Prognosis Diagnosis |
| title | Immunohistochemical staining with non-phospho β-catenin as a diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with extra-peritoneal desmoid-type fibromatosis |
| title_full | Immunohistochemical staining with non-phospho β-catenin as a diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with extra-peritoneal desmoid-type fibromatosis |
| title_fullStr | Immunohistochemical staining with non-phospho β-catenin as a diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with extra-peritoneal desmoid-type fibromatosis |
| title_full_unstemmed | Immunohistochemical staining with non-phospho β-catenin as a diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with extra-peritoneal desmoid-type fibromatosis |
| title_short | Immunohistochemical staining with non-phospho β-catenin as a diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with extra-peritoneal desmoid-type fibromatosis |
| title_sort | immunohistochemical staining with non phospho β catenin as a diagnostic and prognostic tool of cox 2 inhibitor therapy for patients with extra peritoneal desmoid type fibromatosis |
| topic | Non-phospho β-catenin Desmoid-type fibromatosis Meloxicam Prognosis Diagnosis |
| url | http://link.springer.com/article/10.1186/s13000-017-0654-z |
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