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Journal of Thoracic Oncology:
doi: 10.1097/JTO.0000000000000072
Original Articles

Parallel FISH and Immunohistochemical Studies of ALK Status in 3244 Non–Small-Cell Lung Cancers Reveal Major Discordances

Cabillic, Florian PharMD, PhD*†‡; Gros, Audrey PharMD, PhD§; Dugay, Frédéric PharMD*‡‖; Begueret, Hugues MD, PhD; Mesturoux, Laura MD§; Chiforeanu, Dan Cristian MD#; Dufrenot, Leila MD; Jauffret, Vincent; Dachary, Dominique MD§; Corre, Romain MD**; Lespagnol, Alexandra PhD††; Soler, Gwendoline MD, PhD§; Dagher, Julien*‡‖; Catros, Véronique PharMD, PhD*†‡; Le Calve, Michèle PharMD*‡; Merlio, Jean-Philippe MD, PhD§; Belaud-Rotureau, Marc-Antoine PharMD, PhD*‡‖

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Abstract

Introduction:

Anaplastic lymphoma kinase (ALK) rearrangements occur in 1% to 7% of non–small-cell lung cancers (NSCLCs). Crizotinib, an ALK inhibitor, has been demonstrated to provide dramatic clinical benefits in ALK-positive advanced-stage NSCLC. Fluorescent in situ hybridization (FISH) has been established in clinical trials as the standard procedure method for detecting ALK rearrangements. Although the detection of ALK by immunohistochemistry (IHC) has been proposed for the screening of patients, large-scale studies are warranted to validate such a hierarchical approach.

Methods:

In this article, we report the largest series thus far of parallel FISH and IHC ALK testing in 3244 consecutive NSCLC cases analyzed at two independent French centers.

Results:

FISH-positive and/or IHC-positive results were demonstrated in 150 of 3244 cases (4.6%). An imbalanced sex ratio was detected, with women exhibiting a 2.2-fold relative risk for an alteration. Strikingly, only 80 of 150 specimens were classified as ALK positive by both techniques. The specimens with discordant FISH/IHC analyses were FISH-positive/IHC-negative (36), FISH-negative/IHC-positive (19), or FISH-noncontributive/IHC-positive (15). Thus, a single FISH or IHC analysis performed alone would have failed to detect approximately one-fourth of the ALK-positive cases with similar findings in our two centers.

Conclusions:

This study highlights the feasibility of systematic NSCLC testing by both FISH and IHC in routine practice. Many preanalytical factors may account for the apparent discrepancies between both methods, suggesting that hierarchical screening may underscore ALK-positive cases. This significant level of discrepancy supports the need of combined testing to optimize the detection of ALK-inhibitor–eligible patients given that some patients with discordant testing were found to respond to crizotinib.

Copyright © 2013 by the International Association for the Study of Lung Cancer

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