Alturkustani Murad, Yang Bo, Bockoven Crystal, Mahabir Roshan, Shillingford Nick, Schmidt Ryan J, Zhou Shengmei, Warren Mikako, Parham David M, Pawel Bruce, Wang Larry L
Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Transl Pediatr. 2024 Apr 30;13(4):624-633. doi: 10.21037/tp-24-61. Epub 2024 Apr 28.
-associated tumors are heterogeneous and affect several organs. -associated primary intracranial sarcoma is associated with histone H3 trimethylation on lysine 27 (H3K27me3) loss in nucleus by immunohistochemistry.
We explored the H3K27me3 immunostaining pattern in other -associated tumors. Twelve tumors from eleven patients with confirmed mutations (sporadic and germline) data from a pancancer next-generation sequencing panel, and four tumors of pleuropulmonary blastoma (PPB) were retrieved from our database and stained with anti-H3K27me3 antibody.
The H3K27me3 expression in the nucleus showed heterogeneous mosaic loss in neoplastic Sertoli cell components in three of the five cases of moderately to poorly differentiated Sertoli-Leydig cell tumors. Among two tumors of -associated primary intracranial sarcoma, one showed complete loss of H3K27me3 in all neoplastic cells, whereas the other showed mosaic loss in the sarcomatous spindle cells. One -associated tumor with epithelial and mesenchymal differentiation, including pulmonary blastoma and PPB, showed mosaic loss of glandular epithelial and mesenchymal components. Four cases of type II PPB and a single case of type III PPB showed a similar mosaic loss of H3K27me3 staining restricted to large spindle cell components. All other components in all tumors-including Leydig cells; the areas of epithelial, cartilaginous, and rhabdomyomatous differentiation; and all cells of the remaining three cases (one papillary thyroid carcinoma and two cases of PPB type I)-demonstrated retained H3K27me3 staining.
H3K27me3 expression is not universally lost in -associated tumors and thus is not predictive of mutation status. The mosaic regional loss of H3K27me3 immunostaining is consistent in PPB type II and III, which can be a helpful diagnostic marker for these tumors and suggests a similarity to -associated intracranial sarcoma.
-相关肿瘤具有异质性，可累及多个器官。-相关原发性颅内肉瘤通过免疫组化显示与细胞核中赖氨酸27位点的组蛋白H3三甲基化（H3K27me3）缺失有关。
我们探究了其他-相关肿瘤中的H3K27me3免疫染色模式。从我们的数据库中检索了11例经确认有突变（散发性和胚系突变）数据的患者的12个肿瘤（来自泛癌下一代测序面板），以及4例胸膜肺母细胞瘤（PPB）肿瘤，并用抗H3K27me3抗体进行染色。
在5例中分化至低分化的支持-间质细胞瘤的3例中，肿瘤性支持细胞成分的细胞核中H3K27me3表达显示出异质性镶嵌缺失。在2例-相关原发性颅内肉瘤中，1例在所有肿瘤细胞中H3K27me3完全缺失，而另1例在肉瘤样梭形细胞中显示镶嵌缺失。1例具有上皮和间叶分化的-相关肿瘤，包括肺母细胞瘤和PPB，显示腺上皮和间叶成分的镶嵌缺失。4例II型PPB和1例III型PPB显示类似的H3K27me3染色镶嵌缺失，局限于大梭形细胞成分。所有肿瘤中的所有其他成分，包括间质细胞；上皮、软骨和横纹肌瘤样分化区域；以及其余3例（1例乳头状甲状腺癌和2例I型PPB）的所有细胞，均显示H3K27me3染色保留。
H3K27me3表达在-相关肿瘤中并非普遍缺失，因此不能预测-突变状态。H3K27me3免疫染色的镶嵌区域缺失在II型和III型PPB中是一致的，这可能是这些肿瘤的一个有用诊断标志物，并提示与-相关颅内肉瘤相似。
