Claudin 6 Is a Positive Marker for Atypical Teratoid/Rhabdoid Tumors
Claudin 6 Is a Positive Marker for Atypical Teratoid/Rhabdoid Tumors
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DOI：
10.1111/j.1750-3639.2008.00255.x
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发表时间：
2010-01-01
期刊：
影响因子：
6.4
通讯作者：
Handler, Michael H.
中科院分区：
文献类型：
--
作者：
Birks, Diane K.;Kleinschmidt-DeMasters, Bette K.;Handler, Michael H.
非典型畸胎瘤/横纹肌样瘤（AT/RTs）是一种高度侵袭性的儿童脑肿瘤，其特征是横纹肌样细胞的存在和INI1免疫染色阴性（BAF47）。组织发生尚不清楚，诊断可能具有挑战性，因为它们的极端形态和免疫表型异质性。目前，除INI1损失外，未发现其他特征标记。为了寻找AT/RTs中可能的候选蛋白，我们利用Affymetrix基因芯片(R)对9个AT/RTs和124个其他肿瘤样本进行了研究。鉴定出的最独特的基因是claudin 6 (CLDN6)，它是紧密连接的关键成分。CLDN6 mRNA在9个AT/RTs中的8个中有中等或较高的表达，在其他115个肿瘤中的114个中几乎没有表达。AT/RTs的平均表达量比其他样品高38倍。33例肿瘤标本免疫组化（IHC）染色发现7例AT/RTs膜染色阳性，27例脑肿瘤标本26例膜染色阴性。值得注意的是，16例髓母细胞瘤/原始神经外胚层肿瘤均未显示CLDN6的IHC染色。免疫组化染色结果与微阵列检测的mRNA表达水平密切匹配。CLDN6可能是一个有用的阳性标记物，有助于进一步确定AT/RTs的诊断和治疗目的。
Atypical teratoid/rhabdoid tumors (AT/RTs) are highly aggressive pediatric brain tumors characterized by the presence of rhabdoid cells and negative immunostaining for INI1 (BAF47). Histogenesis is unknown and diagnosis can be challenging because of their extreme morphological and immunophenotypic heterogeneity. Currently no signature markers other than INI1 loss have been identified. To search for possible candidate proteins of interest in AT/RTs, Affymetrix GeneChip (R) microarrays were utilized to investigate nine AT/RTs vs. 124 other tumor samples. The most distinctive gene identified was claudin 6 (CLDN6), a key component of tight junctions. CLDN6 showed moderate or higher mRNA expression in eight of nine AT/RTs, with little to no expression in 114 of 115 other tumors. Average expression was 38-fold higher in AT/RTs vs. other samples. Immunohistochemical (IHC) staining of 33 tumor specimens found positive membrane staining in seven of seven AT/RTs, and was negative in 26 of 27 other brain tumor samples. Notably, none of the 16 medulloblastomas/primitive neuroectodermal tumors showed IHC staining for CLDN6. IHC staining results closely matched the level of mRNA expression detected by microarray. CLDN6 may be a useful positive marker to help further identify AT/RTs for diagnostic and treatment purposes.