Anti-CTNNB1 monoclonal antibody, clone FQ701Z Knockout Validated

Sinonasal glomangiopericytoma (SNGP) is a neoplasm arising in the nasal cavity and paranasal sinuses that shows perivascular myoid differentiation. The diagnosis of SNGP may be diagnostically challenging due to a large number of potential mimics. In the present study, we sought to characterize the histological and molecular features of six cases of SNGP found in prior surgical pathology records over a 15-year period. The average age at diagnosis was 48.5 years (range: 31-78 years), and the male-to-female ratio was 1:1. Imaging studies in all six cases demonstrated avidly enhancing, lobulated soft tissue masses in the nasal cavity, extending into the sinuses and nasopharynx. Histologically, the tumors were unencapsulated and composed of a proliferation of closely packed, bland, and uniform spindle cells growing deep to an intact surface respiratory epithelium. The cells were separated by a distinctive vascular network ranging from capillaries to large vascular spaces. All cases demonstrated strong positivity for smooth muscle actin, cyclin D1, CD99, and beta-catenin (100%). Targeted sequencing revealed recurrent CTNNB1 missense mutations in all cases tested. Additionally, TLE1 was positive in all cases which has not been previously reported. No tested cases harbored SS18 translocations. We found that while no single marker resolves immunohistochemical overlap between SNGP and its histologic mimics, an extended immunohistochemical panel that includes beta-catenin, cyclin D1, STATE, smooth muscle actin, pancytokeratin cocktails, S100, and SOX10 helps to support the diagnosis of SNGP in diagnostically challenging cases without the need for molecular studies.

Introduction The majority of desmoid-type fibromatosis (DTF) tumors harbor a beta-catenin mutation, affecting specific codons in CTNNB1 exon 3. S45F tumors are reported to have a higher chance of recurrence after surgery and more resistance to systemic treatments compared to wild-type (WT) and T41A tumors. The aim of this pilot study was to examine the genome-wide DNA methylation profiles of S45F and T41A mutated DTF, to explain the observed differences in clinical behavior between these DTF subtypes. Material and Methods Genome-wide analysis of DNA methylation was performed using MeD-seq on formalin-fixed, paraffin-embedded primary DTF samples harboring a S45F (n = 14) or a T41A (n = 15) mutation. Differentially methylated regions (DMRs) between S45F and T41A DTF were identified and used for a supervised hierarchical cluster analysis. DMRs with a fold-change >= 1.5 were considered to be differentially methylated and differences between S45F and T41A tumors were quantitatively assessed. The effect of DMRs on the expression of associated genes was assessed using an independent mRNA expression dataset. Protein-protein interactions between WT beta-catenin and mutant variants and DNA methyltransferase 1 (DNMT1) were examined by immunoprecipitation experiments. Results MeD-seq analyses indicated 354 regions that displayed differential methylation. Cluster analysis yielded no distinct clusters based on mutation, sex, tumor site or tumor size. A supervised clustering based on DMRs between small (<= 34 mm) and large (>87 mm) DTF distinguished the two groups. Only ten DMRs displayed a fold change of >= 1.5 and six of them were found associated with the following genes: NLRP4, FOXK2, PERM1, CCDC6, NOC4L, and DUX4L6. The effects of DMRs on gene expression yielded a significant difference (p < 0.05) in the expression between S45F and T41A for CCDC6 and FOXK2 but not for all Affymetrix probe-sets used to detect these genes. Immunoprecipitations did not reveal an association of WT beta-catenin or mutant variants with DNMT1. Conclusion This study demonstrated that S45F and T41A DTF tumors did not exhibit gross differences in DNA methylation patterns. This implies that distinct DNA methylation profiles are not the sole determinant for the divergent clinical behavior of these different DTF mutant subtypes.