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Inconsistent results in the analysis of ALK rearrangements in non-small cell lung cancer

Overview of attention for article published in BMC Cancer, August 2016
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Title
Inconsistent results in the analysis of ALK rearrangements in non-small cell lung cancer
Published in
BMC Cancer, August 2016
DOI 10.1186/s12885-016-2646-x
Pubmed ID
Authors

Johanna S. M. Mattsson, Hans Brunnström, Verena Jabs, Karolina Edlund, Karin Jirström, Stephanie Mindus, Linnéa la Fleur, Fredrik Pontén, Mats G. Karlsson, Christina Karlsson, Hirsh Koyi, Eva Brandén, Johan Botling, Gisela Helenius, Patrick Micke, Maria A. Svensson

Abstract

Identification 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. ALK 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. ALK 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. The 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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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 24 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 25%
Student > Ph. D. Student 3 13%
Student > Bachelor 2 8%
Lecturer > Senior Lecturer 2 8%
Lecturer 1 4%
Other 5 21%
Unknown 5 21%
Readers by discipline Count As %
Medicine and Dentistry 10 42%
Pharmacology, Toxicology and Pharmaceutical Science 2 8%
Nursing and Health Professions 2 8%
Social Sciences 1 4%
Biochemistry, Genetics and Molecular Biology 1 4%
Other 0 0%
Unknown 8 33%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 August 2016.
All research outputs
#20,336,685
of 22,881,964 outputs
Outputs from BMC Cancer
#6,506
of 8,326 outputs
Outputs of similar age
#321,923
of 366,897 outputs
Outputs of similar age from BMC Cancer
#199
of 275 outputs
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