H3F3A (Histone 3.3) G34W Immunohistochemistry: A Reliable Marker Defining Benign and Malignant Giant Cell Tumor of Bone.
H3F3A (Histone 3.3) G34W Immunohistochemistry: A Reliable Marker Defining Benign and Malignant Giant Cell Tumor of Bone.
复制标题
DOI：
10.1097/pas.0000000000000859
复制
发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Flanagan AM
中科院分区：
文献类型：
--
作者：
Amary F;Berisha F;Ye H;Gupta M;Gutteridge A;Baumhoer D;Gibbons R;Tirabosco R;O'Donnell P;Flanagan AM
骨巨细胞瘤（GCTB）是一种局部侵袭性关节下肿瘤。最近报道了H3.3 G34 W突变是这种肿瘤类型的特征，我们现在研究了抗组蛋白H3.3 G34 W兔单克隆抗体在各种肿瘤中的灵敏度和特异性，包括GCTB的组织学模拟物，以评估其作为诊断标志物的价值。我们还通过基因型和H3.3 G34 W免疫染色评估原发性恶性骨肿瘤中H3.3 G34突变的发生率。总共检测了3163个肿瘤。213/235例GCTB（90.6%）细胞核H3.3 p.G34W免疫反应阳性。对于罕见的变异p.G34L、M和V，情况并非如此，这些变异最常见于手、髌骨和中轴骨的小骨中。如果从分析中排除这些位点，则在97.8%的GCTB中发现H3.3 G34 W表达。最初被归类为骨肉瘤的恶性骨肿瘤是仅有的显示G34 W表达的其他病变（n=11）。值得注意的是，另外2例先前报告的p.G34R突变的骨肉瘤对抗体无免疫反应性。总共有11/13的这些恶性H3.3突变体肿瘤表现出破骨细胞丰富的成分：当成像可用时，除了一个之外，所有肿瘤都出现在关节下部位。我们认为，关节下原发性恶性骨肉瘤H3.3突变代表真正的恶性GCTB，即使在没有良性GCTB成分。
Giant cell tumor of bone (GCTB) is a locally aggressive subarticular tumor. Having recently reported that H3.3 G34W mutations are characteristic of this tumor type, we have now investigated the sensitivity and specificity of the anti-histone H3.3 G34W rabbit monoclonal antibody in a wide variety of tumors including histologic mimics of GCTB to assess its value as a diagnostic marker. We also determined the incidence of H3.3 G34 mutations in primary malignant bone tumors as assessed by genotype and H3.3 G34W immunostaining. A total of 3163 tumors were tested. Totally, 213/235 GCTB (90.6%) showed nuclear H3.3 p.G34W immunoreactivity. This was not the case for the rare variants, p.G34L, M, and V, which occurred most commonly in the small bones of the hands, patella, and the axial skeleton. If these sites were excluded from the analysis, H3.3 G34W expression was found in 97.8% of GCTB. Malignant bone tumors initially classified as osteosarcomas were the only other lesions (n=11) that showed G34W expression. Notably an additional 2 previously reported osteosarcomas with a p.G34R mutation were not immunoreactive for the antibody. A total of 11/13 of these malignant H3.3-mutant tumors exhibited an osteoclast-rich component: when imaging was available all but one presented at a subarticular site. We propose that subarticular primary malignant bone sarcoma with H3.3 mutations represent true malignant GCTB, even in the absence of a benign GCTB component.