Anaplastic lymphoma kinase immunoreactivity correlates with ALK gene rearrangement and transcriptional up-regulation in non-small cell lung carcinomas
Anaplastic lymphoma kinase immunoreactivity correlates with ALK gene rearrangement and transcriptional up-regulation in non-small cell lung carcinomas
复制标题
DOI：
10.1016/j.humpath.2009.01.012
复制
发表时间：
2009-08-01
期刊：
影响因子：
3.3
通讯作者：
Yi, Eunhee S.
中科院分区：
文献类型：
--
作者：
Boland, Jennifer M.;Erdogan, Sibel;Yi, Eunhee S.
近年来，在非小细胞肺癌中发现了EML 4-ALK融合基因，该基因可能成为一个潜在的治疗靶点。我们通过免疫组化研究了这些肿瘤中间变性淋巴瘤激酶蛋白表达的流行率，并将结果与ALK分子研究的数据相关联。对35例腺癌进行基因表达谱分析，以确定ALK基因上调的病例，其与免疫组化蛋白过表达相关。免疫组化也进行了一个独立的队列，包括150个腺癌和150个鳞状细胞癌，以评估间变性淋巴瘤激酶免疫染色作为筛选工具的效用。通过免疫组织化学对间变性淋巴瘤激酶阳性的肿瘤进行ALK基因座的荧光原位杂交和EML 4-ALK的逆转录酶-聚合酶链反应。通过基因表达谱分析，在2/35例腺癌（6%）中发现ALK转录上调。免疫组化结果显示，2例间变性淋巴瘤激酶阳性，其余33例均为阴性。在独立队列中，150例鳞状细胞癌中1例间变性淋巴瘤激酶免疫染色阳性，150例腺癌中3例阳性。6例间变性淋巴瘤激酶免疫组化阳性患者，荧光原位杂交证实存在ALK基因重排，但EGFR和KRAS突变均阴性。逆转录-聚合酶链反应证实2例患者存在EML 4-ALK融合转录本。总之，间变性淋巴瘤激酶在非小细胞肺癌中的免疫反应性与转录上调、ALK基因座重排和EML 4-ALK融合转录本的存在相关。间变性淋巴瘤激酶免疫组化可作为筛选工具或作为分子技术的替代标记物，以检测这些肿瘤中的EML 4-ALK融合基因。(c)2009 Elsevier Inc. All rights reserved.
Recently, the fusion gene EML4-ALK was identified in non-small cell lung carcinoma, which could be a potential therapeutic target. We investigated the prevalence of anaplastic lymphoma kinase protein expression in these tumors by immunohistochemistry and correlated the results with data from ALK molecular studies. Gene expression profiling was performed on 35 adenocarcinomas to identify cases with ALK gene up-regulation, which was correlated with protein overexpression by immunohistochemistry. Immunohistochemistry was also performed on an independent cohort consisting of 150 adenocarcinomas and 150 squamous cell carcinomas to evaluate the utility of anaplastic lymphoma kinase immunostaining as a screening tool. Florescence in situ hybridization for the ALK locus and reverse transcriptase-polymerase chain reaction for EML4-ALK were performed on tumors positive for anaplastic lymphoma kinase by immunohistochemistry. Transcriptional up-regulation of ALK was identified in 2 (6%) of 35 adenocarcinomas by gene expression profiling. These 2 cases were positive for anaplastic lymphoma kinase by immunohistochemistry, whereas the remaining 33 cases were completely negative. In the independent cohort, anaplastic lymphoma kinase immunostaining was positive in 1 of 150 squamous cell carcinomas and in 3 of 150 adenocarcinomas. The 6 cases positive for anaplastic lymphoma kinase by immunohistochemistry showed evidence of ALK locus rearrangement by florescence in situ hybridization but were negative for EGFR and KRAS mutation. The presence of EML4-ALK fusion transcript was confirmed in 2 cases by reverse transcriptase-polymerase chain reaction. In conclusion, anaplastic lymphoma kinase immunoreactivity in non-small cell lung carcinomas was associated with transcriptional up-regulation, ALK locus rearrangement, and the presence of EML4-ALK fusion transcript. Anaplastic lymphoma kinase immunohistochemistry may have utility as a screening tool or as a surrogate marker for the molecular techniques to detect the EML4-ALK fusion gene in these tumors. (c) 2009 Elsevier Inc. All rights reserved.