ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2026
Diagnostic Utility and Clinicopathologic Associations of Histone H3 Lysine 27 Trimethylation (H3K27me3) Immunohistochemistry for Merkel Cell Carcinoma.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Merkel Cell Carcinoma With Divergent Differentiation-Or Something Else? A Triphasic Cutaneous Carcinoma With Lineage Plasticity.Journal of cutaneous pathology · 2026Review
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5 authors.
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Abstract
Merkel cell carcinoma (MCC) is an aggressive cutaneous tumor that must be distinguished from other cutaneous tumors and metastatic small cell carcinoma (SmCC). Additional diagnostic markers are limited for MCC with immunophenotypic aberrancy. MCC can display immunohistochemical loss of the epigenetic marker histone H3 lysine 27 trimethylation (H3K27me3), but to our knowledge, the diagnostic utility of this observation has not been evaluated. In this study, we investigate H3K27me3 labeling in MCC (n = 195), cutaneous epithelial tumors (n = 48), noncutaneous SmCCs (n = 56), and olfactory neuroblastoma (n = 11), comparing with diagnostic markers, cytokeratin-20, neurofilament, SATB2, and POU4F3. H3K27me3 patterns in MCC included global loss, variable/mosaic labeling, and diffuse labeling. Global loss significantly associated with polyomavirus negativity, squamous atypia, and sarcomatoid change. Tumors with global loss displayed EZHIP expression (9 cases) and SUZ12 mutation (1 case). Low but retained H3K27me3 labeling was associated with longer overall and MCC-specific survival. Diagnostically, H3K27me3 labeling in MCC was significantly lower than potential mimics, and global loss of H3K27me3 was highly specific for MCC; stronger H3K27me3 labeling was not informative. Considering reduced/absent H3K27me3 as favoring MCC, diagnostic performance was similar to SATB2. However, H3K27me3 displayed consistent performance in MCC with challenging immunophenotypes, unlike SATB2. In summary, we expand upon descriptions of H3K27me3 labeling in MCC and characterize patterns of H3K27me3 in other tumor types including SmCCs and olfactory neuroblastoma. Our findings support diagnostic utility for the widely available marker H3K27me3 in MCC, with weaker labeling favoring MCC over mimics in challenging cases.
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