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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