H3F3A mutation in giant cell tumour of the bone is detected by immunohistochemistry using a monoclonal antibody against the G34W mutated site of the histone H3.3 variant
H3F3A mutation in giant cell tumour of the bone is detected by immunohistochemistry using a monoclonal antibody against the G34W mutated site of the histone H3.3 variant
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DOI：
10.1111/his.13190
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发表时间：
2017-07-01
期刊：
影响因子：
6.4
通讯作者：
Barth, Thomas F. E.
中科院分区：
文献类型：
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作者：
Lueke, Julian;von Baer, Alexandra;Barth, Thomas F. E.
目的：骨巨细胞瘤（GCTB）是一种主要长骨肿瘤，其特征为 H3F3A 突变 G34W。肿瘤富含巨细胞的形态对传统诊断提出了挑战，这种形态与其他含有巨细胞的骨病变重叠。最近，一种针对H3F3A突变的特异性单克隆抗体已经产生。我们的目的是在一组含有巨细胞的病变上测试该抗体。方法和结果：我们使用该抗体分析了 22 名 H3F3A 突变的 GCTB，其中包括两名复发患者；为了进行比较，我们分析了一组 36 例 H3F3A 野生型富含巨细胞的骨和软组织病变，其中包括 1 例棕色肿瘤、6 例动脉瘤性骨囊肿 (ABC)、6 例软骨母细胞瘤、5 例非骨化纤维瘤、2 例纤维异常增生、9 例腱鞘巨细胞瘤、1 例富含巨细胞肉瘤和 6 例腱鞘巨细胞瘤。 骨肉瘤。此外，在22例突变病例中，我们纳入了1例GCTB，其中2例复发并发生肺转移；该患者接受了核因子 kappa B (RANK) 配体抗受体激活剂地诺单抗治疗。我们发现，所有 22 个 H3F3A 突变的 GCTB 在肿瘤成分中均显示出强烈的核 H3.3 G34W 染色，而破骨细胞巨细胞呈阴性。 36 个 H3F3A 野生型病变呈阴性。用狄诺塞麦治疗的 GCTB 显示 H3.3 G34W 阳性肿瘤细胞减少，破骨巨细胞减少，并伴有基质和类骨质形成。结论：我们得出结论，阳性 H3.3 G34W 染色是检测 H3F3A 突变 GCTB 的特异性且灵敏的方法。狄诺塞麦治疗导致病变的病理形态，其特征是产生基质和类骨质的 H3.3 G34W 阴性基质细胞。
Aims: Giant cell tumour of the bone (GCTB) is a neoplasm predominantly of long bones characterized by the H3F3A mutation G34W. Conventional diagnosis is challenged by the tumour's giant cell-rich morphology, which overlaps with other giant cell-containing lesions of the bone. Recently, a monoclonal antibody specific for the H3F3A mutation has been generated. Our aim was to test this antibody on a cohort of giant cell-containing lesions.Methods and results: We used the antibody for analysis of 22 H3F3A-mutated GCTB, including two patients with recurrences; for comparison we analysed a cohort of 36 H3F3A wild-type giant cell-rich lesions of the bone and soft tissue, containing one brown tumour, six aneurysmal bone cysts (ABC), six chondroblastomas, five non-ossifying-fibromas, two fibrous dysplasias, nine tenosynovial giant cell tumours, one giant cell-rich sarcoma and six osteosarcomas. Furthermore, among the 22 mutated cases, we included one GCTB with two recurrences and lung metastases; the patient was treated with the anti-receptor activator of nuclear factor kappa B (RANK) ligand denosumab. We show that all 22 H3F3A-mutated GCTB display strong nuclear H3.3 G34W staining in the neoplastic component, while the osteoclastic giant cells are negative. 36 H3F3A wildtype lesions are negative. The GCTB treated with denosumab revealed a reduction in the H3.3 G34W-positive tumour cells and a decrease in osteoclastic giant cells accompanied by matrix and osteoid formation.Conclusions: We conclude that positive H3.3 G34W staining is a specific and sensitive method for detection of H3F3A-mutated GCTB. Denosumab treatment leads to a pathomorphosis of the lesion characterized by matrix and osteoid producing H3.3 G34W-negative stromal cells.