Anaplastic lymphoma kinase immunoreactivity correlates with ALK gene rearrangement and transcriptional up-regulation in non-small cell lung carcinomas

被引:136
作者
Boland, Jennifer M.
Erdogan, Sibel
Vasmatzis, George
Yang, Ping [2 ]
Tillmans, Lori S.
Johnson, Michele R. Erickson
Wang, Xiaoke
Peterson, Lisa M.
Halling, Kevin C.
Oliveira, Andre M.
Aubry, Marie Christine
Yi, Eunhee S. [1 ]
机构
[1] Mayo Clin & Mayo Fdn, Mayo Med Sch, Div Anat Pathol, Dept Lab Med & Pathol, Rochester, MN 55905 USA
[2] Mayo Clin & Mayo Fdn, Mayo Med Sch, Dept Med, Rochester, MN 55905 USA
关键词
ALK; NSCLC; FISH; EML4-ALK fusion transcript; EML4-ALK FUSION GENE; RANDOMIZED PHASE-II; PLUS CISPLATIN; CANCER; IDENTIFICATION; INHIBITOR; EFFICACY;
D O I
10.1016/j.humpath.2009.01.012
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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.
引用
收藏
页码:1152 / 1158
页数:7
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