48. ALK tissue FISH in lung cancer: The MDACC experience

      The clinical cytogenetics laboratory at MD Anderson Cancer Center routinely provides the FDA approved ALK fluorescence in situ hybridization (ALK FISH) assay to assist in identifying patients with lung cancer for tyrosine kinase inhibitor (TKI) therapy. From November 2012 to November 2019, 5919 specimens from 5478 individuals were tested. Among them, 236 specimens (3.99%) out of 215 individuals (3.92%) were positive for ALK rearrangement; 164 specimens (2.77%) out of 166 individuals (2.94%) had an inconclusive result, while all the others were tested negative. For specimen with an inconclusive result, analytical causes were excluded, while pre-analytical causes, such as origins (lung, lymph nodes, bone, brain, liver, body fluids and so on), types (surgical biopsy vs. fine needle biopsy, FNB), sources (from MDACC vs. outside institutes including international institutes), ages of samples might play a role. Among 401 individuals tested for ≥2 times, 31 (7.73%) had at least one inconclusive result, and 18 (4.49%) exhibited inconsistent results (positive to negative or vice versa) while the others presented either a consistent positive (n=19, 4.74%) or consistent negative (n=333, 83.04%) result. The potential causes for the inconsistent results vary among them, including the pre-analytical causes, pre- vs. post-TKI therapy sampling, tumor heterogeneity between primary and metastatic lung cancer and so on. Approximately 40% (7/18) exhibited a positivity of ≤ 30%, and 3 were positive and one was negative for EML4-ALK fusion by RNA-seq. According to the new ALK testing guidelines, ALK status in a specimen can be tested by different methods and platforms, and an increased frequency of inconsistent results can be assumed. Therefore, the implementation of a practical diagnostic algorithm for precise detection of ALK status in each specimen is vital for clinical management of lung cancer.
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