A rational diagnostic algorithm for the identification of ALK rearrangement in lung cancer: a comprehensive study of surgically treated Japanese patients.
A rational diagnostic algorithm for the identification of ALK rearrangement in lung cancer: a comprehensive study of surgically treated Japanese patients.
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DOI：
10.1371/journal.pone.0069794
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Suzuki K
中科院分区：
文献类型：
--
作者：
Takamochi K;Takeuchi K;Hayashi T;Oh S;Suzuki K
EML 4-ALK融合基因仅在一小部分（2-6%）非小细胞肺癌中发现。目前迫切需要建立一种合理的诊断算法来识别这种罕见但重要的肺癌融合。我们对360例手术切除的肺癌患者进行了EGFR/KRAS突变和ALK重排的综合分析。通过3种分析检查ALK重排：多重逆转录-PCR、荧光原位杂交（FISH）和免疫组织化学（IHC）与嵌入抗体增强聚合物法。使用评分系统进行IHC（iScore）。一个测试集（202例肺癌患者）被用来提出一个诊断算法。该诊断算法在158例EGFR和KRAS突变阴性腺癌患者中得到验证。 在试验集中的2例患者（1.0%）中发现了ALK重排，两种腺癌的EGFR和KRAS突变均为阴性。FISH和RT-PCR结果完全吻合。最高iScore 3仅见于2例阳性病例。提出了一种诊断算法：IHC筛查ALK重排，然后进行确证性FISH。在验证集中，8例（5.1%）iScore 3，FISH阳性，而其他病例iScore 0，FISH阴性。通过IHC筛查ALK重排，然后进行确证性FISH是合理的诊断算法。如果需要，可以根据EGFR和KRAS突变状态选择患者进行ALK重排筛查。
EML4-ALK fusion gene is found in only a small subset (2–6%) of non-small cell lung cancer. There is an urgent need to establish a rational diagnostic algorithm to identify this rare but important fusion in lung cancer. We performed a comprehensive analysis of EGFR/KRAS mutation and ALK rearrangement in a total of 360 surgically resected lung cancers. ALK rearrangement was examined by 3 analyses: multiplex reverse transcription-PCR, fluorescent in situ hybridization (FISH), and immunohistochemistry (IHC) with the intercalated antibody-enhanced polymer method. A scoring system was used for IHC (iScore). A test set (202 patients with unselected lung cancer) was used for proposing a diagnostic algorithm. This diagnostic algorithm was validated in 158 patients with EGFR and KRAS mutation-negative adenocarcinoma. ALK rearrangement was identified in 2 patients (1.0%) from the test set and both adenocarcinomas were negative for EGFR and KRAS mutations. The results of FISH and RT-PCR were completely matched. The highest iScore 3 was found only in the 2 positive cases. A diagnostic algorithm was proposed: IHC screening for ALK rearrangement followed by confirmatory FISH. In the validation set, 8 cases (5.1%) had iScore 3 and were positive for FISH, while the other cases had iScore 0 and were negative for FISH. Screening for ALK rearrangement by IHC followed by confirmatory FISH is a rational diagnostic algorithm. If needed, patients may be selected for screening ALK rearrangement by their EGFR and KRAS mutation status.
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影响因子：
158.5
作者：
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通讯作者：
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