Biomedical Engineering Reference
In-Depth Information
rearrangement in NSCLC is a relatively rare event with
the incidence in largely unselected series ranging anywhere from
2% to 7% [9-11, 29, 32-34, 37, 44]. In the initial description of the
EML4-ALK
The
ALK
oncogene, 5 out of 75 lung tumors (6.7%) had evidence
of the
rearrangement by RT-PCR [9]. Similarly, but in a select
population of East Asian never smokers with adenocarcinomas,
Sun
ALK
et al.
noted that 5.8% (3 out of 52) harbored the
EML4-ALK
fusion, second after the more common oncogenic driver mutation
in
that was harbored in 78.8% of patients [45]. Knowledge of
the clinicopathologic features associated with
EGFR
-positive
tumors has enabled researchers to enrich for this defined subset of
patients. In the study by Shaw
EML4-ALK
in which patients were selected
based on features associated with
et al.
mutations including
female gender, Asian ethnicity, never/light smoking history and
adenocarcinoma histology, 13% were found to harbor the
EGFR
ELM4-
ALK
fusion [40]. Within the group of patients who were never/light
smokers, the frequency of
was 22% and when looking at
the subgroup of patients who were both never/light smokers and
EGFR
EML4-ALK
wild-type the frequency increased to 33%. Thus, one in three
patients with NSCLC may harbor the
fusion if the patient
population is enriched with characteristics associated with the
EML4-ALK
EGFR
mutation but who are actually
EGFR
wild-type.
16.4
Methods of Detection
The accurate identification of a patient with NSCLC positive for
the ALK gene rearrangement using any given screening technique
is critical for both outcome assessment and therapy. ALK gene
rearrangements may be detected in tumor specimens using four
techniques: DNA sequencing, reverse transcriptase-PCR (RT-PCR),
immunohistochemistry (IHC), and fluorescence
hybridization
(FISH). None of these assays have yet proven to be easily adopted
by diagnostic molecular pathology laboratories. DNA sequencing is
considered the “gold standard,” but the optimal screening method
between the other three techniques still needs validation. Although
these methods are highly specific and extensively validated in
anaplastic large cell lymphoma [46], each has significant challenges
when applied to the detection of ALK rearrangements in lung
adenocarcinomas.
in situ
