Claudin-6 is a nonspecific marker for malignant rhabdoid and other pediatric tumors.
Claudin-6 is a nonspecific marker for malignant rhabdoid and other pediatric tumors.
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DOI：
10.1097/pas.0b013e31822cfa7e
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Judkins AR
中科院分区：
文献类型：
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作者：
Sullivan LM;Yankovich T;Le P;Martinez D;Santi M;Biegel JA;Pawel BR;Judkins AR
Claudins是紧密连接蛋白，Claudin-6(CLDN6)的表达主要限于胚胎和胎儿。以往报道的基因表达芯片分析显示，与其他中枢神经系统肿瘤和肉瘤相比，不典型畸胎样横纹肌样肿瘤(AT/RT)中CLDN6的表达水平升高。然而，对于CLDN6在中枢神经系统肿瘤中的表达，免疫组织化学方法存在着相互矛盾的数据。基于胎儿和青少年对照，我们建立了膜SAING作为评估CLDN6表达的一种特异和可重复性的方法。然后，我们使用组织芯片(TMA)评估了一大组(257例)儿童肿瘤，包括：47例恶性横纹肌样瘤(MRT)，31例AT/RT和16例非CNS MRT；67例小圆形蓝细胞肿瘤(Wilms瘤10例，胚胎性横纹肌肉瘤10例，神经母细胞瘤10例，滑膜肉瘤10例，肝母细胞瘤9例，泡状横纹肌肉瘤9例，尤文肉瘤9例)；143例中枢神经系统肿瘤(髓母细胞瘤24例，毛细胞性星形细胞瘤21例，星形细胞瘤II/III级14例，神经节胶质瘤13例，胶质母细胞瘤12例，室管膜瘤12例，脉络丛肿瘤11例，脑膜瘤10例，胚胎发育不良神经上皮瘤8例，少突胶质细胞瘤8例，颅咽管瘤4例，生殖细胞瘤2例，PNET 2例，中枢神经细胞瘤2例)。CLDN6在12/31(39%)AT/RT和7/16(44%)非CNS MRT、5/10(50%)Wilms瘤、1/9(11%)肝母细胞瘤、2/2(100%)生殖细胞瘤、1/2(50%)CNS PNET、1/24(4%)髓母细胞瘤和1/10(10%)脑膜瘤中表达。11例脉络丛肿瘤中，10例(91%)可见根尖染色，无同心膜性染色。虽然CLDN6在AT/RT和MRT中都有表达，但它不是一个特异的生物标记物，因为它在其他多种儿科中枢神经系统和软组织肿瘤中都有表达。
Claudins are tight junction proteins with claudin-6 (CLDN6) expression mostly restricted to embryonic and fetal life. Previously reported gene expression microarray analysis showed an increased level of CLDN6 in atypical teratoid rhabdoid tumors (AT/RT) compared to other CNS tumors and sarcomas. However, there is conflicting data on expression of CLDN6 by immunohistochemistry in CNS tumors. We established membranous saining as a specific and reproducible method for evaluating CLDN6 expression based on fetal and adolescent controls. We then evaluated a large group (257) of pediatric tumors using tissue microarrays (TMA) including: 47 malignant rhabdoid tumors (MRT), (31 AT/RT and 16 non-CNS MRT); 67 small round blue cell tumors (10 Wilms tumors, 10 embryonal rhabdomyosarcomas, 10 neuroblastomas, 10 synovial sarcomas, 9 hepatoblastomas, 9 alveolar rhabdomyosarcomas and 9 Ewings sarcomas); and 143 CNS tumors (24 medulloblastomas, 21 pilocytic astrocytomas, 14 astrocytomas grade II/III, 13 gangliogliomas, 12 glioblastomas, 12 ependymal tumors, 11 choroid plexus tumors, 10 meningiomas, 8 dysembryoplastic neuroepithelial tumors, 8 oligodendrogliomas, 4 craniopharyngiomas, 2 germinomas, 2 PNET, 2 central neurocytomas). CLDN6 expression was seen in 12/31 (39%) AT/RT and 7/16 (44%) non-CNS MRT, 5/10 (50%) Wilms tumor, 1/9 (11%) hepatoblastomas, 2/2 (100%) germinomas, 1/2 (50%) CNS PNET, 1/24 (4%) medulloblastomas and 1/10 (10%) meningiomas. Ten of 11 (91%) choroid plexus tumors showed apical staining, but no concentric membranous staining. While CLDN6 is expressed in both AT/RT and MRT, it is not a specific biomarker as it is expressed in a variety of other pediatric CNS and soft tissue tumors.