ArticleBMC cancer2016
Inconsistent results in the analysis of ALK rearrangements in non-small cell lung cancer.
Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 36 citations in OpenAlex.
- Spatial distribution of tertiary lymphoid structures in the molecular and clinical context of non-small cell lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Comparison of ROS1-rearrangement detection methods in a cohort of surgically resected non-small cell lung carcinomas.Translational lung cancer research · 2022Article
- Targeting Anaplastic Lymphoma Kinase in GI Primary Malignancies.JCO precision oncology · 2022Article
- TGF-β-mediated epithelial-mesenchymal transition and tumor-promoting effects in CMT64 cells are reflected in the transcriptomic signature of human lung adenocarcinoma.Scientific reports · 2021Article
- SMPD3-ALK: A novel ALK fusion gene in lung adenocarcinoma.Clinical genetics · 2021Article
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- Clinicopathological value of ErbB2 gene and protein expression in osteochondroma.Acta orthopaedica et traumatologica turcica · 2020Article
- Fluorescence in Situ Hybridization (FISH) for Detecting Anaplastic Lymphoma Kinase (International journal of molecular sciences · 2019Review
- Article
- ALK-rearrangement in non-small-cell lung cancer (NSCLC).Thoracic cancer · 2018Review
- PD-L1 immunohistochemistry in clinical diagnostics of lung cancer: inter-pathologist variability is higher than assay variability.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2017Article
- Article
- Integrative analysis of genome-wide gene copy number changes and gene expression in non-small cell lung cancer.PloS one · 2017Article
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIdentification of targetable EML4-ALK fusion proteins has revolutionized the treatment of a minor subgroup of non-small cell lung cancer (NSCLC) patients. Although fluorescence in situ hybridization (FISH) is regarded as the gold standard for detection of ALK rearrangements, ALK immunohistochemistry (IHC) is often used as screening tool in clinical practice. In order to unbiasedly analyze the diagnostic impact of such a screening strategy, we compared ALK IHC with ALK FISH in three large representative Swedish NSCLC cohorts incorporating clinical parameters and gene expression data.
methodsALK rearrangements were detected using FISH on tissue microarrays (TMAs), including tissue from 851 NSCLC patients. In parallel, ALK protein expression was detected using IHC, applying the antibody clone D5F3 with two different protocols (the FDA approved Ventana CDx assay and our in house Dako IHC protocol). Gene expression microarray data (Affymetrix) was available for 194 patients.
resultsALK rearrangements were detected in 1.7 % in the complete cohort and 2.0 % in the non-squamous cell carcinoma subgroup. ALK protein expression was observed in 1.8 and 1.4 % when applying the Ventana assay or the in house Dako protocol, respectively. The specificity and accuracy of IHC was high (> 98 %), while the sensitivity was between 69 % (Ventana) and 62 % (in house Dako protocol). Furthermore, only 67 % of the ALK IHC positive cases were positive with both IHC assays. Gene expression analysis revealed that 6/194 (3 %) tumors showed high ALK gene expression (≥ 6 AU) and of them only three were positive by either FISH or IHC.
conclusionThe overall frequency of ALK rearrangements based on FISH was lower than previously reported. The sensitivity of both IHC assays was low, and the concordance between the FISH and the IHC assays poor, questioning current strategies to screen with IHC prior to FISH or completely replace FISH by IHC.
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