Low expression of H3K27me3 is associated with poor prognosis in conventional chordoma

Wei, Jie; Wu, Jianfeng; Yin, Zhiyong; Li, Xia; Liu, Yixiong; Wang, Yingmei; Wang, Zhe; Xu, Chao; Fan, Linni

doi:10.3389/fonc.2022.1048482

Cited by 3 publications

(1 citation statement)

References 35 publications

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“…Loss of 1p36 and 9p specifically has been associated with decreased overall survival [ 25 ]. Reduced expression of H3K27me3, associated with poor prognosis in other tumors, has also been demonstrated in conventional chordoma [ 30 ].…”

Section: Chordoma Genetics and Prognosticationmentioning

confidence: 99%

Chordoma: Genetics and Contemporary Management

Desai,

Pelargos,

Dunn

2024

IJMS

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Chordomas, arising from notochord remnants, are rare neoplasms with aggressive growth patterns despite their histologically low-grade nature. This review explores their embryological origins, molecular markers like brachyury, and genetic alterations driving pathogenesis. Diagnosis relies on advanced imaging and biopsy confirmation due to overlapping features with chondrosarcoma. The WHO classification distinguishes conventional, dedifferentiated, and poorly differentiated chordomas, each with distinct prognostic implications. Recent genomic analyses uncovered recurrent mutations in PI3K signaling pathways and chromatin remodeling genes, informing prognostic models. Surgery remains the cornerstone of treatment, though adjuvant radiation complements surgical resection. Although chordomas are generally considered refractory to medical therapy, emerging targeted molecular strategies show potential promise in ongoing trials. This review aims to provide a concise yet comprehensive overview of chordomas, guiding clinicians in diagnosis, treatment, and prognostication for improved patient outcomes.

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Section: Chordoma Genetics and Prognosticationmentioning

confidence: 99%

Chordoma: Genetics and Contemporary Management

Desai,

Pelargos,

Dunn

2024

IJMS

View full text Add to dashboard Cite

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Prognostic value of immunohistochemical staining for H3K27me3 and EZH2 in astrocytoma, IDH-mutant

Onishi,

Yamasaki,

Amatya

et al. 2024

J Neurooncol

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Background H3 histone 27 lysine (H3K27) trimethylation (H3K27me3), which is catalyzed by enhancer of zeste homolog 2 (EZH2), regulates gene expression through epigenetic mechanisms. H3K27me3 is used as a diagnostic marker for diffuse midline glioma and as a surrogate marker to distinguish posterior fossa ependymoma A and B. However, the clinical significance of the EZH2–H3K27me3 axis in astrocytoma, IDH-mutant has not been reported, prompting this investigation. Methods Thirty-three patients with astrocytoma, IDH-mutant treated at our institute were included in this study. Immunohistochemistry (IHC) targeting H3K27me3, H3K27M, EZH2, EZH inhibitory protein, IDH1-R132H, p53, ATRX, Ki-67, and MTAP was performed. Kaplan–Meier analysis and Cox regression analysis were performed to analyze the correlations of overall survival (OS) and progression-free survival (PFS) with various factors, including age, World Health Organization (WHO) grade, the extent of resection, and immunohistochemical results. Results The mean patient age was 40.6 ± 11.0 years. IHC for H3K27me3 was positive in 19 patients and negative in 14 patients. The WHO grade and Ki-67 index were significantly higher in the H3K27me3-positive group (p = 0.004 and p = 0.024, respectively). OS and PFS were significantly shorter in the H3K27me3-positive group (p = 0.002 and p = 0.026, respectively). Furthermore, the H3K27me3 and EZH2 double-positive group was associated with a higher WHO grade and higher Ki-67 index (p = 0.001 and p = 0.024, respectively). In the analysis of patients with WHO grade 2/3, double positivity for H3K27me3 and EZH2 was linked to significantly shorter OS and PFS (p = 0.0053 and p = 0.0048, respectively). Conclusion Positivity for H3K27me3, especially double positivity for H3K27me3 and EZH2, could be a poor prognostic factor for astrocytoma, IDH-mutant. These results suggest the utility of H3K27me3 and EZH2 as candidate markers for estimating the malignancy of astrocytoma, IDH-mutant.

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