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

BackgroundImmunohistochemical 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.MethodsBetween 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.ResultsOf 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).ConclusionsNuclear 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.

Are We Benign? What Can Wnt Signaling Pathway and Epithelial to Mesenchymal Transition Tell Us about Intracranial Meningioma Progression

“…Immunohistochemical analysis of mutated samples was performed using two antibodies that monitor total β-catenin (phosphorylated and non-phosphorylated) and the non-phosphorylated or active form of β-catenin (NON-P β-catenin) showed. The NON-P antibody does not detect β-catenin phosphorylated at S33/S37/T41, which was also showed in the study by Sakai et al [ 69 ]. Although in some samples with mutations, which harbor a change in amino acid sequence or premature cessation of protein synthesis resulting in the protein lacking phosphorylation sites for kinases in its N-terminal domain, which is recognized by destruction complex [ 66 ], the active form of β-catenin was weak (83.3%) or moderate in signal (16.7%).…”

Recurrent Aggressive Fibromatosis Coexisting With Papillary Carcinoma Thyroid – Case Report

“…Mutation inhibits phosphorylation of β-catenin, which protects β-catenin from degradation by the APC complex, resulting in nuclear accumulation of β-catenin, where it binds to TCF/LEF family of transcription factors and turns on the number of target genes. 4 β-catenin mutation is also detected in the case of papillary thyroid carcinoma with desmoid-type fibromatosis. However, the β-catenin mutation was not detected in our case.…”

A large and aggressive fibromatosis in the axilla: a rare case report and review of the literature

“… 6 In particular, immunohistochemistry (IHC) detection of β-catenin expression can be used as one feature supportive of the diagnosis of AF. 7 – 9 More recently, FDG PET/CT has been widely applied for clinical staging. It should be emphasized, however, that the increased SUV values can be noted in both benign- and malignant-behaving tumors.…”