Combined Screening Suggested to Better Detect ALK Rearrangements in Samples from Non-Small-Cell Lung Cancer Patients

Anaplastic lymphoma kinase (ALK) rearrangements occur in 1% to 7% of non-small-cell lung cancers (NSCLCs), but nearly 25% of samples from NSCLC patients with ALK rearrangements were not identified when analyzed by either fluorescent in situ hybridization (FISH) or immunohistochemistry (IHC).

Investigators at the Université de Rennes (France) reported results from a large series of parallel FISH and IHC ALK testing in 3244 consecutive NSCLC cases analyzed at two independent French centers. The results revealed FISH-positive and/or IHC-positive results in 150 of the 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.

The drug crizotinib, an ALK inhibitor, has been demonstrated to provide dramatic clinical benefits in ALK-positive advanced-stage NSCLC. “Data on crizotinib response in patients who have been diagnosed differently by FISH and IHC are still preliminary,” said first author Dr. Florian Cabillic, a researcher at the Université de Rennes. “Thus, until large-scale studies in patients under therapy with crizotinib determine which testing is the most relevant to predict responses to ALK inhibition, our data support the need to routinely perform both analyses because of the difficulty in detecting the chimeric ALK protein in NSCLC and the presence of false-negative cases for each method.”

The study was published in the March 2014 issue of the Journal of Thoracic Oncology.

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