Background
Selection of NSCLC patients for targeted therapy is currently based upon
the presence of sensitizing mutations in EGFR and EML4/ALK
translocations. The heterogeneity of molecular alterations in lung
cancer has led to the ongoing discovery of potential biomarkers and
targets in order to improve survival.
Aim
This study aimed to detect alterations in EGFR, KRAS, BRAF, PIK3CA,
MET-gene copy number and ALK rearrangements in a large cohort of 956
NSCLC patients of Hellenic origin using highly sensitive techniques and
correlations with clinicopathological characteristics.
Results
Mutations were detected in EGFR 10.6%(101 out of 956 samples), KRAS
26.5% (191 out of 720 samples), BRAF 2.5% (12 out of 471 samples),
PIK3CA 3.8% (7 out of 184 samples), MET gene amplification was detected
in 18% (31 out of 170) and ALK rearrangements in 3.7% (4 out of 107
samples). EGFR mutations were detected in exon 19 (61.4% of mutant
cases), exon 21 p.Leu858Arg (19.8%), exon 20 (15.8%), exon 18 (2.9%)
and were correlated with gender histology, smoking status and TTF1
staining. p.Thr790Met mutant cases (3.9%) displayed concurrent
mutations in exons 19 or 21. Negative TTF-1 staining showed strong
negative predictive value for the presence of EGFR mutations. KRAS
mutations were associated with histology, the most common mutation being
p.Gly12Cys (38%).
Discussion
In conclusion, only 89 patients were eligible for EGFR-TKIs and ALK
inhibitors therapy, whereas 257 patients showed other alterations,
highlighting the necessity for a detailed molecular profiling
potentially leading to more efficient individualized therapies for NSCLC
patients