Reliability Assurance of Detection of EML4-ALK Rearrangement in Non–Small Cell Lung Cancer: The Results of Proficiency Testing in China

Abstract

IntroductionCurrently, several approaches are being used to detect echinoderm microtubule associated protein like 4 gene (EML4)–anaplastic lymphoma receptor tyrosine kinase gene (ALK) rearrangement, but the performance of laboratories in China is unknown. To evaluate the proficiency of different laboratories in detecting EML4-ALK rearrangement, we organized a proficiency test (PT). MethodsWe prepared formalin-fixed, paraffin-embedded samples derived from the xenograft tumor tissue of three non–small cell lung cancer cell lines with different EML4-ALK rearrangements and used PTs to evaluate the detection performance of laboratories in China. ResultsWe received results from 94 laboratories that used different methods. Of the participants, 75.53% correctly identified all samples in the PT panel. Among the errors made by participants, false-negative errors were likely to occur. According to the methodology applied, 82.86%, 76.67%, 77.78%, and 66.67% of laboratories using reverse transcriptase polymerase chain reaction, fluorescence in situ hybridization, next-generation sequencing, and immunohistochemical analysis, respectively, could analyze all the samples correctly. Moreover, we have found that the laboratories' genotyping capacity is high, especially for variant 3. ConclusionOur PT survey revealed that the performance and methodological problems of laboratories must be addressed to further increase the reproducibility and accuracy of detection of EML4-ALK rearrangement to ensure reliable results for selection of appropriate patients.