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首页> 外文期刊>Lung cancer: Journal of the International Association for the Study of Lung Cancer >Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC): Results of a multi-centre ALK-testing
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Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC): Results of a multi-centre ALK-testing

机译：非小细胞肺癌（NSCLC）的间变性淋巴瘤激酶（ALK）基因重排：多中心ALK测试的结果

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Background: The reliable identification of non-small cell lung cancers (NSCLC) with chromosomal breaks in the gene of the anaplastic lymphoma kinase (ALK) is crucial for the induction of therapy with ALK-inhibitors. In order to ensure a reliable detection of ALK-breaks by means of fluorescence in situ hybridization (FISH) testing, round robin tests are essential. In preparation of a nation (German)-wide round robin test we initiated a pre-testing phase involving 8 experts in FISH-diagnostics to identify NSCLC cases (n=10) with a pre-tested ALK-status. In addition, ALK immunohistochemistry (IHC) was performed to assess ALK protein expression. Material and methods: Sections derived from a tissue microarray, each consisting of 3 cores from 10 NSCLC cases, were independently tested for ALK protein expression by IHC and genomic ALK-breaks by FISH involving 8 institutes of pathology. Based on a pre-screening, 5 cases were identified to be clearly ALK-break negative, whereas the remaining 5 cases were ALK-break positive including one case with low percentage (20%) of positive cells. The latter had been additionally tested by RT-PCR. Results: The 5 unequivocal ALK-break negative NSCLC were almost consistently scored negative by means of FISH and IHC by all 8 experts. Interestingly, 4 of the 5 cases with pre-defined ALK-breaks revealed homogenous FISH results whereas IHC for the detection of ALK protein expression showed heterogeneous results. The remaining case (low number of ALK-break positive cells) was scored negative by 3 experts and positive by the other 5. RT-PCR revealed the expression of an EML4-ALK fusion gene variant 1. Conclusion: ALK-break negative NSCLC cases revealed concordant homogeneous results by means of FISH and IHC (score 0-1) by all 8 experts. Discordant FISH results were raised in one ALK-break positive case with a low number of affected tumor cells. The remaining 4 ALK-break positive cases revealed concordant FISH data whereas the ALK-IHC revealed very diverse results. The cases with concordant FISH results provide an excellent basis for round robin ALK-FISH testing. As long as standardized ALK-IHC protocols are missing, ALK protein expression cannot by regarded as the method of choice for identification of patients eligible for treatment with ALK inhibitors.
机译：背景：通过间变性淋巴瘤激酶（ALK）基因的染色体断裂来可靠地鉴定非小细胞肺癌（NSCLC）对于诱导用ALK抑制剂进行治疗至关重要。为了确保通过荧光原位杂交（FISH）测试可靠地检测ALK断裂，循环测试是必不可少的。在准备整个国家（德国）的循环测试时，我们启动了由8位FISH诊断专家组成的预测试阶段，以鉴定具有预先测试的ALK状态的NSCLC病例（n = 10）。另外，进行ALK免疫组织化学（IHC）以评估ALK蛋白表达。材料和方法：来源于组织微阵列的切片，每个切片由10个NSCLC病例的3个核心组成，由IHC独立检测ALK蛋白表达，并由FISH检测涉及8个病理研究所的基因组ALK断裂。根据预筛查，鉴定出5例明显为ALK断裂阴性，而其余5例为ALK断裂阳性，包括1例阳性细胞百分比低（20％）。后者已经通过RT-PCR另外测试。结果：所有8位专家通过FISH和IHC几乎一致地将5个明确的ALK断裂阴性NSCLC评分为阴性。有趣的是，在5个预定义的ALK断裂病例中，有4个显示出均一的FISH结果，而用于检测ALK蛋白表达的IHC显示了异类结果。其余病例（ALK断裂阳性细胞数量少）被3名专家评为阴性，其他5名阳性。RT-PCR显示EML4-ALK融合基因变体1的表达。结论：ALK断裂阴性NSCLC病例通过所有8位专家的FISH和IHC（得分0-1）揭示了一致的均一结果。在一例ALK断裂阳性病例中受影响的肿瘤细胞数量少，FISH结果不一致。其余4例ALK断裂阳性病例显示一致的FISH数据，而ALK-IHC则显示非常多样的结果。 FISH结果一致的案例为循环ALK-FISH测试提供了极好的依据。只要缺少标准的ALK-IHC方案，ALK蛋白表达就不能被视为鉴定适合用ALK抑制剂治疗的患者的选择方法。

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