Related Experiment Video
Updated: Apr 25, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Multicenter ALK testing in non-small-cell lung cancer: results of a round robin test
Maximilian von Laffert1, Roland Penzel, Peter Schirmacher
1*Institute of Pathology, Humboldt University Berlin, Campus Charité Mitte, Charité Universitätsmedizin, Berlin, Germany; and †Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Background:
The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has recently received approval for the treatment of patients with locally advanced or metastatic ALK-positive non-small-cell lung cancer (NSCLC). As the therapeutic prescription postulates the detection of ALK rearrangements, reliable diagnostic approaches are of utmost importance. With this study, we present the data of the first German ALK-round robin test based on genomic DNA in situ hybridization (ISH). The application of immunohistochemistry (IHC) for ALK protein detection was optional and not required for certification.
Methods:
Two tissue microarrays, each consisting of the same 10 NSCLC but in different arrangement of the cases, were generated (five unequivocally ALK-positive and five unequivocally ALK-negative cases). ISH-based results and optional IHC data had to be submitted within 10 working days. A successful participation (certification) was reached if at least 19 of the 20 possible points were scored (2 points for a correct case classification).
Results:
Fifty-three of 59 participants (89.8%) provided their data for ISH-ALK detection within the submission period. Thirty-two of 53 participants (60.3%) received at least 19 points required for certification. Remarkably, the range of cells with aberrant ALK signal configuration was broad in ALK-negative (0-13%) and in ALK-positive cases (15-95%). Thirty-five participants supported the round robin test with optional ALK IHC results, which displayed a great heterogeneity in the ALK ISH-positive cases.
Conclusion:
In essence, our ALK ISH round robin test clearly demonstrates that there is accumulating need for improvement of ALK testing. Although ISH may be regarded as a well-established procedure, its broad application in a diagnostic setting is challenging and requires standardized methods and harmonized interpretation to achieve sound results for therapeutic decisions. The same is true for ALK IHC which, however if standardized, might improve the diagnostic approach.
Insights
This study evaluated ALK testing accuracy in non-small-cell lung cancer using genomic DNA in situ hybridization (ISH). Results show a need for standardized methods to ensure reliable ALK detection for targeted therapies.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, is approved for ALK-positive non-small-cell lung cancer (NSCLC).
- Accurate ALK rearrangement detection is crucial for guiding crizotinib therapy.
- This study reports on the first German proficiency test for ALK detection using genomic DNA in situ hybridization (ISH).
Purpose of the Study:
- To assess the accuracy and reliability of ALK testing in NSCLC using ISH.
- To evaluate the performance of diagnostic laboratories in a round robin test setting.
- To identify areas for improvement in ALK testing methodologies for clinical practice.
Main Methods:
- A German round robin test was conducted using two tissue microarrays with 10 NSCLC cases (5 ALK-positive, 5 ALK-negative).
- Participants used genomic DNA in situ hybridization (ISH) for ALK detection; immunohistochemistry (IHC) was optional.
- Certification required scoring at least 19 out of 20 possible points.
Main Results:
- Out of 59 participants, 53 (89.8%) submitted ISH-ALK data; 32 (60.3%) achieved certification.
- A wide range of aberrant ALK signal configurations was observed in both ALK-negative (0-13%) and ALK-positive (15-95%) cases.
- Optional ALK IHC results from 35 participants showed heterogeneity, particularly in ALK ISH-positive cases.
Conclusions:
- The ALK ISH round robin test highlights a significant need for improved ALK testing accuracy in NSCLC diagnostics.
- Standardization of methods and interpretation is essential for reliable ISH results in a clinical setting.
- Standardized ALK IHC could potentially enhance diagnostic approaches for ALK-positive NSCLC.
More Related Videos
10:35A Blood-based Test for the Detection of ROS1 and RET Fusion Transcripts from Circulating Ribonucleic Acid Using Digital Polymerase Chain Reaction
Published on: April 5, 2018
08:49Exosomal miRNA Analysis in Non-small Cell Lung Cancer NSCLC Patients' Plasma Through qPCR: A Feasible Liquid Biopsy Tool
Published on: May 27, 2016