A new method of assessing ALK gene rearrangement in lung cancer appears to be a relatively easy and inexpensive way to determine whether a person with lung cancer can benefit from the ALK inhibitor crizotinib.
Accurate determination of ALK rearrangement in persons with lung cancer is important, particularly when determining their eligibility for crizotinib therapy. Patients with ALK rearrangement have been found to respond well to the drug, which is currently in clinical trials. Although fluorescence in situ hybridization (FISH) has been regarded as the gold-standard method for identifying ALK rearrangement, this technique requires a fluorescence microscope, and the signals are labile and fade over time.
Investigators compared FISH with a newly developed ALK chromogenic in situ hybridization (CISH) in assessing ALK gene rearrangement in 465 samples of non-small cell lung cancer. CISH uses a conventional peroxidase-base reaction and standard bright field light microscope to detect gene copy status.
CISH was used to assess ALK rearrangement in 449 patients (96.6%), identifying ALK rearrangement in 18 (4.0%). FISH was used to assess ALK rearrangement in 453 patients (97.4%), identifying it in 19 (4.2%).
Nearly all of the CISH cases—443 of the 449 (95.3%)—had results matching the corresponding FISH results:17 rearranged, 425 wild types, and 1 discordant case.
“CISH is a highly reproducible and practical method to detect ALK gene rearrangement and correlated well with ALK protein expression,” concluded the researchers in the Journal of Thoracic Oncology (2011;6:1359-1366). “Because CISH allows a concurrent analysis of histological features of the tumors and gene rearrangement, it appears to be a useful method in determining ALK gene rearrangement.”