ALK-rearranged lung cancer in Chinese: a comprehensive assessment of clinicopathology, IHC, FISH and RT-PCR.

ALK-rearranged lung cancer in Chinese: a comprehensive assessment of clinicopathology, IHC, FISH and RT-PCR.
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中国ALK重排肺癌:临床病理学、IHC、FISH和RT-PCR的综合评估

DOI:
10.1371/journal.pone.0069016
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Chen H
Chen H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li Y;Pan Y;Wang R;Sun Y;Hu H;Shen X;Lu Y;Shen L;Zhu X;Chen H

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大约3%-7%的非小细胞肺癌存在间变性淋巴瘤激酶(ALK)基因融合,构成了一种新的肺癌分子亚型,对ALK抑制剂Crizotinib有反应。虽然以前的研究已经评估了ALK重排的肺癌,但对中国人肺癌的综合分析还没有得到很好的评估。在此,我们通过荧光原位杂交(FISH)、免疫组织化学(IHC)和逆转录聚合酶链式反应(RT-PCR)对大量手术切除的肺癌组织中的44例ALK重排标本进行了鉴定。44例ALK重排肺癌均为腺癌,2例伴有局限性鳞状细胞癌成分。目的:分析ALK重排肺腺癌的临床病理特征。我们的数据显示,筛状结构、突出的细胞外粘液和任何类型的粘液细胞模式对预测ALK重排可能是敏感的或特异的。我们用鱼作为标准检测方法。我们比较了FISH、RT-PCR和IHC的ALK重排准确性。RT-PCR可以同时确定ALK融合伙伴和融合变异体,但似乎无法检测到涉及ALK基因的所有易位。值得注意的是,使用D5F3抗体(细胞信号技术)的IHC显示出比ALK1抗体(DAKO)更高的敏感性和特异性。因此,我们得出结论,IHC仍然是诊断ALK重排的一种经济有效的技术,D5F3可能是临床上最佳的抗体筛选方法。
Approximately 3–7% of non-small cell lung cancers harbor an anaplastic lymphoma kinase (ALK) gene fusion, constituting a new molecular subtype of lung cancer that responds to crizotinib, an ALK inhibitor. Although previous studies have evaluated ALK-rearranged lung cancers, the comprehensive analysis of lung cancer in Chinese has not well assessed. Herein, we identified 44 cases of ALK-rearranged samples by fluorescent in-situ hybridization (FISH), immunohistochemistry (IHC), and reverse transcription polymerase chain reaction (RT-PCR) in a large number of surgically resected lung cancers. All 44 ALK-rearranged lung cancers were adenocarcinomas, with 2 cases having additional focal squamous components. The goal was to analyse the clinicopathological features of ALK-rearranged lung adenocarcinomas. Our data showed that a cribriform structure, prominent extracellular mucus and any type of mucous cell pattern may be either sensitive or specific to predict an ALK rearrangement. We used FISH as the standard detection method. We compared the ALK rearrangement accuracy of FISH, RT-PCR and IHC. RT-PCR could define both the ALK fusion partner and the fusion variant, but seemed unable to detect all translocations involving the ALK gene. It is noteworthy that IHC using the D5F3 antibody (Cell Signaling Technology) showed higher sensitivity and specificity than the ALK1 antibody (Dako). Therefore, we conclude that IHC remains a cost-effective and efficient technique for diagnosing ALK rearrangements and that D5F3 can be the optimal screening antibody in clinical practice.
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