Atypical Teratoid Rhabdoid Tumors (ATRTs): The British Columbia's Children's Hospital's Experience, 1986-2006
Atypical Teratoid Rhabdoid Tumors (ATRTs): The British Columbia's Children's Hospital's Experience, 1986-2006
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DOI：
10.1111/j.1750-3639.2011.00561.x
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发表时间：
2012-09-01
期刊：
影响因子：
6.4
通讯作者：
Dunham, Christopher
中科院分区：
文献类型：
--
作者：
Fleming, Adam J.;Hukin, Juliette;Dunham, Christopher
由于非典型畸胎样横纹肌样肿瘤(ATRT)可能类似于小圆形蓝色细胞肿瘤(SRBCT)，我们重新审视了我们的ATRT经验，重点是INI-1免疫组织化学(IHC)。19862006年间所有发生在我们研究所的高级别儿童脑肿瘤均接受了INI-1免疫组化检查。对INI-1免疫阴性病例的临床病理资料进行复习。对INI-1免疫阴性病例的子集进行了额外的遗传、表观遗传学和IHC分析(包括对INI-1和CLDN6的询问)。12个INI-1 IHC阴性肿瘤被回顾性鉴定，其中只有两个以前被诊断为ATRT。总体而言，临床病理和遗传学数据支持所有12个病例都代表ATRT的断言。出乎意料的是，发现了三名长期幸存者(4.2年、7.0年和8.5年)。正如假设的那样，尽管在某些病例中进行了大体全切除，但畸胎样和横纹肌样的组织学特征相对较少。甲基化特异性聚合酶链式反应(MSP)显示所有病例和所测试的基因启动子(即MGMT、HIC1、MLH3和RASSF1)的甲基化模式一致；值得注意的是，所有病例都显示未甲基化的MGMT启动子。我们的数据表明，原始的非横纹肌样组织表型在ATRT中很常见，并强调了INI-1 IHC的诊断重要性。表观遗传学上，MGMT启动子在ATRT中通常是非甲基化的，这表明潜在的基于替莫唑胺的化疗效果可能有限。
As atypical teratoid rhabdoid tumors (ATRTs) may mimic small round blue cell tumors (SRBCT), we reexamined our ATRT experience focusing upon INI-1 immunohistochemistry (IHC). All high-grade pediatric brain tumors occurring from 19862006 at our institution underwent INI-1 IHC. Clinicopathologic data from each INI-1 immunonegative case were reviewed. Additional genetic, epigenetic and IHC analyses (including interrogation of INI-1 and CLDN6) were performed on a subset of the INI-1 immunonegative cases. Twelve INI-1 IHC negative tumors were identified retrospectively, of which only two previously carried the diagnosis of ATRT. Overall, the clinicopathologic and genetic data supported the assertion that all 12 cases represented ATRT. Unexpectedly, three long-term survivors (4.2, 7.0 and 8.5 years) were identified. As hypothesized, teratoid and rhabdoid histologic features were relatively infrequent despite gross total resections in some cases. Methylation specific polymer chain reaction (PCR) (MSP) revealed a uniform methylation pattern across all cases and gene promoters tested (ie, MGMT, HIC1, MLH3 and RASSF1); notably, all cases demonstrated unmethylated MGMT promoters. Our data demonstate that a primitive non-rhabdoid histophenotype is common among ATRTs and highlights the diagnostic importance of INI-1 IHC. Epigenetically, the MGMT promoter is usually unmethylated in ATRT, suggesting that potential temozolomide-based chemotherapy may be of limited efficacy.