Concordance of immunohistochemistry and fluorescent in situ hybridization for anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer: Results from a multicenter study in China

Crizotinib, a small molecular anaplastic lymphoma kinase (ALK) inhibitor, was approved by the Chinese Food and Drug Administration for ALK positive non-small cell lung cancer (NSCLC) patients in 2013. Although clinical trials have used the Vysis fluorescent in situ hybridization (FISH) ALK Break-Apart Assay to determine ALK status, the test is only available in limited laboratories and is technically challenging. A standardized and cost effective methodology is therefore in high demand. The aim of this study was to compare the diagnostic accuracy of Vysis FISH ALK Break-Apart Assay and VENTANA ALK (D5F3) immunohistochemistry (IHC) assay for detection of echinoderm microtubule associated protein like4-anaplastic lymphoma kinase (EML4-ALK) rearrangement in NSCLC. FISH and IHC analyses were performed on 1174 cases collected from three provincial cancer hospitals in China. The patient cohort included cases of NSCLC, small cell lung cancer (SCLC), normal lung specimens and other tumor types. We found that IHC assay is highly concordance with FISH assay, showing a positive percent agreement rate of 99.30%, negative percent agreement rate of 99.22%, and overall agreement rate of 99.23%. Our results thus suggest that the VENTANA ALK (D5F3) IHC assay is a valuable tool for the screening of patients with ALK rearrangement in clinical practice.