Loss of SMARCB1/INI1 expression in poorly differentiated chordomas
Loss of SMARCB1/INI1 expression in poorly differentiated chordomas
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DOI：
10.1007/s00401-010-0767-x
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发表时间：
2010-12-01
影响因子：
12.7
通讯作者：
Vogel, Hannes
中科院分区：
文献类型：
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作者：
Mobley, Bret C.;McKenney, Jesse K.;Vogel, Hannes
脊索瘤是一种恶性肿瘤，通常发生在中轴脊柱，主要影响成年人。当脊索瘤发生在儿科患者时，它们更可能显示出不寻常的组织学特征和攻击性行为。我们注意到在骶骨低分化脊索瘤的索引病例中没有SMARCB 1/INI 1的免疫组化表达，这使我们进一步检查SMARCB 1/INI 1的表达，以及在另外3个斜坡低分化脊索瘤、10个典型脊索瘤和8个非典型畸胎瘤/横纹肌样肿瘤（AT/RT）中的短尾畸形（一种高度特异性的脊索分化标记物）的表达。所有4例低分化脊索瘤和所有AT/RT细胞核均无SMARCB 1/INI 1表达，而10例典型脊索瘤细胞核SMARCB 1/INI 1免疫反应阳性。所有10例典型和4例低分化脊索瘤均表达短尾畸形;所有8例AT/RT均为短尾畸形免疫阴性。利用染色体22 q上SMARCB 1/INI 1位点附近的FISH探针对所有低分化脊索瘤进行细胞遗传学评价。四个低分化脊索瘤中的三个有证据表明该区域缺失FISH。SMARCB 1/INI 1基因序列分析使用福尔马林固定石蜡包埋组织在所有情况下，没有观察到点突变。总之，所有低分化脊索瘤在这一系列表现出SMARCB 1/INI 1表达的情况下，并可靠地区分AT/RT，临床上通过其特征性原发部位的起源和病理学上通过强核短尾表达。我们的研究结果揭示了SMARCB 1/INI 1在具有侵袭性特征的脊索瘤亚组中的可能作用。
Chordomas are malignant neoplasms that typically arise in the axial spine and primarily affect adults. When chordomas arise in pediatric patients they are more likely to display unusual histological features and aggressive behavior. We noted the absence of SMARCB1/INI1 expression by immunohistochemistry in an index case of poorly differentiated chordoma of the sacrum, leading us to further examine SMARCB1/INI1 expression as well as that of brachyury, a highly specific marker of notochordal differentiation, in 3 additional poorly differentiated chordomas of the clivus, 10 typical chordomas, and 8 atypical teratoid/rhabdoid tumors (AT/RTs). All 4 poorly differentiated chordomas and all AT/RTs lacked nuclear expression of SMARCB1/INI1, while the 10 typical chordomas maintained strong nuclear SMARCB1/INI1 immunoreactivity. All 10 typical and 4 poorly differentiated chordomas expressed brachyury; all 8 AT/RTs were brachyury immunonegative. Cytogenetic evaluation utilizing FISH probes near the SMARCB1/INI1 locus on chromosome 22q was also performed in all of the poorly differentiated chordomas in this series. Three of the four poorly differentiated chordomas had evidence for deletion of this region by FISH. Analysis of the SMARCB1/INI1 gene sequence was performed using formalin-fixed paraffin-embedded tissue in all cases and no point mutations were observed. In summary, all poorly differentiated chordomas in this series showed the absence of SMARCB1/INI1 expression, and were reliably distinguished from AT/RTs, clinically by their characteristic primary sites of origin and pathologically by strong nuclear brachyury expression. Our findings reveal a likely role for SMARCB1/INI1 in a subset of chordomas with aggressive features.