Authors
Akira Satou, Kanae Yoshikawa, Ikki Mitsuda, Akari Iwakoshi, Makoto Minoshima, Masaharu Gunji, Hideki Murakami, Joaquim Carreras, Haruka Ikoma, Naoya Nakamura, Toyonori Tsuzuki, Masanori Sato, Kennosuke Karube
Published in
Pathology international. Volume 76. Issue 8. Pages e70167.
Abstract
Histone methyltransferase EZH2 is essential for germinal center formation, and gain-of-function mutations of EZH2 occur in approximately 20% of follicular lymphomas (FLs). Although EZH2 inhibitors are used for relapsed/refractory EZH2-mutated (EZH2mut) FLs, their clinicopathological characteristics remain incompletely understood. We assessed the EZH2 Y646 mutation by Sanger sequencing in 301 FLs and identified mutations in 17% (50/301). Compared with EZH2 wild-type (EZH2wt), EZH2mut FL showed a significantly higher proportion aged > 60 years (p = 0.033). Pathologically, EZH2mut FL more frequently exhibited clear neoplastic follicles (p < 0.0001) and grater interfollicular tumor cell distributions highlighted by CD20 immunohistochemistry (p < 0.0001). These cases also more often showed the typical FL immunophenotype (CD10+, BCL2+, BCL6+) (p = 0.027) and BCL2 rearrangement (p = 0.0060). Gene expression profiling revealed enrichment of TNF-α/NF-κB signaling in EZH2wt FL, whereas EZH2mut FL showed upregulation of cell-cycle programs, particularly the G2/M checkpoint. Concordance of EZH2 mutation status between primary and relapsed lesions was 94% (33/35). Even at relapse, EZH2mut FL retained its characteristic pathological features, including clear follicles and high interfollicular spread of tumor cells. In conclusion, EZH2mut FL exhibits distinctive clinicopathological and molecular features that may help identify patients most likely to benefit from EZH2-targeted therapy.
PMID:
42633616
Bibliographic data and abstract were imported from PubMed on 24 Aug 2026.
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