Publication

Status quo of ALK testing in lung cancer: results of an EQA scheme based on in-situ hybridization, immunohistochemistry, and RNA/DNA sequencing

Journal Paper/Review - Jun 25, 2021

Units
Keywords
PubMed
Doi
Link
Contact

Citation
Jurmeister P, Vollbrecht C, Jöhrens K, Aust D, Behnke A, Stenzinger A, Penzel R, Endris V, Schirmacher P, Fisseler-Eckhoff A, Neumann J, Kirchner T, Büttner R, Merkelbach-Bruse S, Kreipe H, Jonigk D, Jochum W, Rodriguez R, Dietel M, Horst D, Hummel M, von Laffert M. Status quo of ALK testing in lung cancer: results of an EQA scheme based on in-situ hybridization, immunohistochemistry, and RNA/DNA sequencing. Virchows Arch 2021; 479:247-255.
Project
Type
Journal Paper/Review (English)
Journal
Virchows Arch 2021; 479
Publication Date
Jun 25, 2021
Issn Print
Issn Electronic
1432-2307
Pages
247-255
Publisher
Brief description/objective

With this external quality assessment (EQA) scheme, we aim to investigate the diagnostic performance of the currently available methods for the detection of ALK alterations in non-small cell lung cancer on a national scale, namely, in situ hybridization (ISH), immunohistochemistry (IHC), and RNA/DNA sequencing (NGS). The EQA scheme cohort consisted of ten specimens, including four ALK positive and six ALK negative samples, which were thoroughly pretested using IHC, ISH, and RNA/DNA NGS. Unstained tumor sections were provided to the 57 participants, and the results were retrieved via an online questionnaire. ISH was used by 29, IHC by 38, and RNA/DNA sequencing by 19 participants. Twenty-eight institutions (97%) passed the ring trial using ISH, 33 (87%) by using IHC, and 18 (95%) by using NGS. The highest sensitivity and interrater agreement (Fleiss ' kappa) was observed for RNA/DNA sequencing (99%, 0.975), followed by ISH (94%, 0.898) and IHC (92%, 0.888). However, the proportion of samples that were not evaluable due to bad tissue quality was also higher for RNA/DNA sequencing (4%) compared with ISH (0.7%) and IHC (0.5%). While all three methods produced reliable results between the different institutions, the highest sensitivity and concordance were observed for RNA/DNA sequencing. These findings encourage the broad implementation of this method in routine diagnostic, although the application might be limited by technical capacity, economical restrictions, and tissue quality of formalin-fixed samples.