Clinicopathological, Molecular, and DNA Methylation Analysis of Ossifying Fibromyxoid Tumors Delineates the ZC3H7B::BCOR Subset as a Distinct Entity
Modern Pathology, cilt.39, sa.8, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 39 Sayı: 8
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.modpat.2026.101025
- Dergi Adı: Modern Pathology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CINAHL, EMBASE, MEDLINE, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest)
- Anahtar Kelimeler: methylation profiling, ossifying fibromyxoid tumor, sarcoma with BCOR genetic alterations, TFE3, ZC3H7B::BCOR
- Hacettepe Üniversitesi Adresli: Evet
Özet
Ossifying fibromyxoid tumor (OFMT) is a rare mesenchymal neoplasm of uncertain lineage of differentiation driven by a broad spectrum of gene fusions. It manifests primarily in soft tissues of the extremities. In this study, we performed a comprehensive clinicopathological, molecular-genetic, and epigenetic analysis of 70 cases of OFMT, with a specific focus on rare fusion subtypes, particularly ZC3H7B::BCOR, PHF1::TFE3, and MEAF6::PHF1. In addition, we included 7 tumors with novel fusions, namely, AFF3::PHF1, PHF1::KLF15, PHF1::PRKAG1, CREBBP::PHF1, EPC1::BMI1, MEAF6::BCOR, and EP300::BCORL1. The clinicopathological characteristics revealed a correlation between specific fusions and aggressive clinical behavior; notably, tumors with ZC3H7B::BCOR fusions were always classified as morphologically atypical or malignant and were associated with significantly higher recurrence and metastatic rates compared with other fusion groups, particularly EP400::PHF1. Immunohistochemical analysis further revealed a distinct immunophenotype in the ZC3H7B::BCOR group. Whereas immunopositivity for cytokeratins and myogenic markers was observed in approximately one-quarter and more than one-third of OFMT cases overall, respectively, ZC3H7B::BCOR–rearranged tumors were negative for both. In contrast, the majority showed immunopositivity for pan-Trk. Additionally, DNA methylation profiling distinguished ZC3H7B::BCOR–rearranged cases from other fusion-positive OFMT cases. The former group clustered closely with a subset of high-grade endometrial stromal sarcomas. This study supports the recognition of ZC3H7B::BCOR–positive tumors as a distinct clinicopathological entity, contributing to the refined molecular taxonomy of this neoplasm.