Discordance between FISH, IHC, and NGS Analysis of ALK Status in Advanced Non–Small Cell Lung Cancer (NSCLC): a Brief Report of 7 Cases

BACKGROUND: Anaplastic lymphoma kinase (ALK) rearrangement represents a landmark in the targeted therapy of non–small cell lung cancer (NSCLC). Immunohistochemistry (IHC) is a sensitive and specific method to detect ALK protein expression, possibly an alternative to fluorescence in situ hybridization (FISH). In this study, the concordance of FISH and IHC to determine ALK status was evaluated, particularly focusing on discordant cases. In our discordant cases, a coexistent complex pattern (deleted, split, and amplified/polysomic) of ALK gene was observed by FISH analysis. These complex rearranged cases were not detectable by IHC, and it could be speculated that more complex biological mechanisms could modulate protein expression. These data highlight the role of IHC and underscore the complexity of the genetic pattern of ALK. It could be crucial to consider these findings in order to best select patients for anti-ALK treatment in daily clinical practice. READ ARTICLE

Translational Oncology
DOI:10.1016/j.tranon.2018.11.006

Authors: Anna Scattone, Annamaria Catino, Laura Schirosi, Lucia Caldarola, Stefania Tommasi, Rosanna Lacalamita, Elisabetta Sara Montagna, Domenico Galetta, Gabriella Serio, Francesco Alfredo Zito, Anita Mangia