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Title: [Expression of H3.3 G34W mutant-specific antibody in giant cell tumors of bone and its diagnostic value].
Author: Wang X, Wu N, Zhang RS, Wei X, Ji RH, Ma HH, Zhou XJ, Rao Q.
Journal: Zhonghua Bing Li Xue Za Zhi; 2020 Feb 08; 49(2):116-121. PubMed ID: 32074722.
Abstract:
Objective: To investigate the expression of H3.3 G34W mutant-specific antibody in giant cell tumors of bone (GCTB), and its value in the diagnosis of GCTB. Methods: Immunohistochemical (IHC) EnVision method was used to detect the expression of H3.3 G34W mutant-specific antibody and p63 in 83 GCTBs, 18 aneurysmal bone cysts, 23 chondroblastomas and 28 osteosarcomas diagnosed at Nanjing Jinling Hospital from June 2001 to April 2019. Results: Among the 83 cases of GCTB, 69 cases (69/83, 83.1%) expressed H3.3 G34W. H3.3 G34W expression was found exclusively in the mononuclear cell population with strong and diffuse nuclear staining. H3.3 G34W was expressed in 55 of 57 (96.5%) cases of GCTB in long bones, but only 14 of 26 (53.8%) cases of non-long bone GCTB. All recurrent (9/9)/metastatic GCTB (2/2), post-denosumab GCTB (3/3), primary malignant GCTB (3/3) and secondary malignant GCTB (5/5) also expressed H3.3 G34W. H3.3 G34W was negative in all aneurysmal bone cysts and chondroblastomas. H3.3 G34W was positive in 3 of 28(10.7%) cases of osteosarcomas, and giant cell-rich osteosarcoma(GCRO) was the only histological subtype of osteosarcoma that expressed H3.3 G34W. p63 was expressed in 71.1%(59/83) of GCTB, while the positive rates of p63 in aneurysmal bone cysts,chondroblastomas and osteosarcomas were 3/18, 43.5% (10/23) and 21.4% (6/28) respectively. The sensitivity and specificity of H3.3 G34W mutant-specific antibody in the diagnosis of GCTB were 83.1% and 95.7%. Conclusions: H3.3 G34W mutant-specific antibody is a highly sensitive and specific marker for GCTB and helpful for the diagnosis of GCTB and its variants. The limitation of this antibody is that as a mall number of GCTB harbor G34 mutation other than G34W, and thus that cannot be detected. The incidental expression of H3.3 G34W mutant protein in osteosarcoma could be a potential diagnostic dilemma, and the results of H3.3 G34W IHC staining needs careful interpretation. 目的： 探讨H3.3 G34W突变抗体在骨巨细胞瘤（GCTB）中的表达情况及其对GCTB诊断的作用。 方法： 收集解放军东部战区总医院病理科2001年6月至2019年4月诊断的83例GCTB、18例动脉瘤样骨囊肿、23例软骨母细胞瘤和28例骨肉瘤病历资料，采用免疫组织化学EnVision法检测H3.3 G34W突变抗体和p63的表达情况。 结果： 83例GCTB中，69例（69/83）显示H3.3 G34W阳性，阳性率为83.1%，H3.3 G34W染色仅见于单核肿瘤细胞的细胞核，呈弥漫强阳性表达。H3.3 G34W在57例发生于长骨的GCTB中表达的阳性率为96.5%（55/57），而在26例发生于非长骨的GCTB中阳性率仅为53.8%（14/26）。所有复发（9/9）或转移性GCTB（2/2）、denosumab治疗后GCTB（3/3）、原发性恶性GCTB（3/3）和继发性恶性GCTB（5/5）均为H3.3 G34W阳性。所有动脉瘤样骨囊肿和软骨母细胞瘤均为H3.3 G34W免疫组织化学染色阴性。28例骨肉瘤中，H3.3 G34W的阳性率为10.7%（3/28）。富于巨细胞的骨肉瘤（GCRO）是骨肉瘤中唯一表达H3.3 G34W的组织学亚型。p63在71.1%（59/83）的GCTB中表达，而在动脉瘤样骨囊肿、软骨母细胞瘤和骨肉瘤中的阳性比例分别为3/18、43.5%（10/23）和21.4%（6/28）。H3.3 G34W突变抗体在GCTB诊断中的灵敏度和特异度分别为83.1%和95.7%。 结论： H3.3 G34W突变抗体是诊断GCTB高度灵敏和特异的标志物，有助于与具有相似形态学的骨肿瘤的鉴别。该抗体的局限性是少数存在G34突变但不是G34W突变的GCTB不能被检测出。骨肉瘤中H3.3 G34W突变蛋白的偶然表达可能是一个潜在的诊断难题，该免疫组织化学结果需谨慎解释。.

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