Immunohistochemistry for histone H3G34W and H3K36M is highly specific for giant cell tumor of bone and chondroblastoma, respectively, in FNA and core needle biopsy.
Immunohistochemistry for histone H3G34W and H3K36M is highly specific for giant cell tumor of bone and chondroblastoma, respectively, in FNA and core needle biopsy.
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DOI：
10.1002/cncy.22000
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发表时间：
2018-08
影响因子：
3.4
通讯作者：
Qian X
中科院分区：
文献类型：
--
作者：
Schaefer IM;Fletcher JA;Nielsen GP;Shih AR;Ferrone ML;Hornick JL;Qian X
在有限的活检中诊断富含巨细胞的骨肿瘤可能具有挑战性。H3组蛋白家族成员3A（H3 F3 A）（G34 W/V/R/L）突变存在于大多数骨巨细胞瘤（GCT）中，H3组蛋白家族成员3B（H3 F3 B）（K36 M）突变存在于几乎所有成软骨细胞瘤中，但在组织学模拟中不存在。突变特异性免疫组织化学（IHC）对手术切除的GCT和软骨母细胞瘤具有高度特异性。本研究的目的是验证H3 G34 W和H3 K36 M IHC在细针穿刺和空芯针活检标本中诊断富含巨细胞骨肿瘤的价值。使用抗组蛋白H3.3 G34 W和K36 M的单克隆抗体对骨GCT（26例，包括2例恶性病例）、佩吉特病GCT（1例）、软骨母细胞瘤（8例）、囊性骨囊肿（7例）和骨肉瘤（13例）进行免疫组化，其中细针穿刺和/或空芯针穿刺活检标本来自2个机构。对所有4个H3 G34 W IHC阴性GCT进行H3 F3 A和H3 F3 B桑格测序。26例GCT中有22例（85%）H3 G34 W的IHC阳性，所有组织学模拟物均为阴性。H3 K36 M在所有8例软骨母细胞瘤中均为阳性，在所有组织学模拟中均为阴性。在158份样本中，152份（96%）活检和手术标本的IHC结果一致。测序鉴定了各1例IHC阴性GCT中的交替H3 F3 A G34 L和G34 V突变，但在其余2例病例中未发现突变。在富含巨细胞的骨肿瘤中，H3 G34 W和H3 K36 M IHC分别对GCT和软骨母细胞瘤具有高度特异性，可用于在有限的活检中确认诊断。交替H3 F3 A突变的存在解释了骨病例GCT亚组中H3 G34 W IHC阴性。
Diagnosing giant cell-rich bone tumors can be challenging on limited biopsies. H3 histone family member 3A (H3F3A) (G34W/V/R/L) mutations are present in the majority of giant cell tumors (GCTs) of bone and H3 histone family member 3B (H3F3B) (K36M) mutations are present in nearly all chondroblastomas, but are absent in histologic mimics. Mutation-specific immunohistochemistry (IHC) is highly specific for GCT and chondroblastoma in surgical excisions. The objective of the current study was to validate H3G34W and H3K36M IHC in the diagnosis of giant cell-rich bone tumors on fine-needle aspiration and core needle biopsy specimens. IHC was performed using monoclonal antibodies against histone H3.3 G34W and K36M in GCTs of bone (26 cases, including 2 malignant cases), GCT of Paget disease (1 case), chondroblastoma (8 cases), aneurysmal bone cyst (7 cases), and osteosarcoma (13 cases) with available fineneedle aspiration and/or core needle biopsy specimens from 2 institutions. H3F3A and H3F3B Sanger sequencing was performed on all 4 H3G34W IHC-negative GCTs. IHC for H3G34W was positive in 22 of 26 GCTs (85%) and negative in all histologic mimics. IHC for H3K36M was positive in all 8 chondroblastomas and negative in all histologic mimics. IHC results were concordant between biopsy and surgical specimens in 152 of 158 samples (96%). Sequencing identified alternate H3F3A G34L and G34V mutations in 1 IHC-negative GCT each, but no mutation was found in the remaining 2 cases. H3G34W and H3K36M IHC is highly specific for GCT and chondroblastoma, respectively, among giant cell-rich bone tumors, and is useful for confirming the diagnosis in limited biopsies. The presence of alternate H3F3A mutations accounts for the H3G34W IHC negativity in a subset of GCT of bone cases.
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影响因子：
3.5
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
Koelsche, Christian;Schrimpf, Daniel;Mechtersheimer, Gunhild
通讯作者：
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影响因子：
30.8
作者：
Behjati, Sam;Tarpey, Patrick S.;Presneau, Nadege;Scheipl, Susanne;Pillay, Nischalan;Van Loo, Peter;Wedge, David C.;Cooke, Susanna L.;Gundem, Gunes;Davies, Helen;Nik-Zainal, Serena;Martin, Sancha;McLaren, Stuart;Goodie, Victoria;Robinson, Ben;Butler, Adam;Teague, Jon W.;Halai, Dina;Khatri, Bhavisha;Myklebost, Ola;Baumhoer, Daniel;Jundt, Gernot;Hamoudi, Rifat;Tirabosco, Roberto;Amary, M. Fernanda;Futreal, P. Andrew;Stratton, Michael R.;Campbell, Peter J.;Flanagan, Adrienne M.
通讯作者：
Flanagan, Adrienne M.