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Updated: Apr 6, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Comprehensive Molecular Analysis of NSCLC; Clinicopathological Associations
Ilenia Chatziandreou1, Panagiota Tsioli1, Stratigoula Sakellariou1
1First Department of Pathology, Laikon General Hospital, Athens University Medical School, Athens, Greece.
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.
Insights
This study analyzed molecular alterations in 956 non-small cell lung cancer (NSCLC) patients. While few were eligible for current targeted therapies, many had other actionable mutations, emphasizing the need for comprehensive molecular profiling.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Current non-small cell lung cancer (NSCLC) targeted therapy relies on EGFR mutations and ALK translocations.
- Molecular heterogeneity in NSCLC necessitates discovery of new biomarkers and therapeutic targets to improve patient survival.
Purpose of the Study:
- To detect alterations in EGFR, KRAS, BRAF, PIK3CA, MET gene copy number, and ALK rearrangements in 956 Hellenic NSCLC patients.
- To correlate these molecular findings with clinicopathological characteristics.
Main Methods:
- Utilized highly sensitive techniques for molecular analysis.
- Analyzed a large cohort of 956 NSCLC patients of Hellenic origin.
Main Results:
- Detected EGFR mutations in 10.6%, KRAS in 26.5%, BRAF in 2.5%, PIK3CA in 3.8%, MET amplification in 18%, and ALK rearrangements in 3.7%.
- EGFR mutations were common in exon 19 and 21; KRAS mutations, primarily p.Gly12Cys, were associated with histology.
- Negative TTF-1 staining predicted absence of EGFR mutations.
Conclusions:
- Only 89 patients were eligible for EGFR-TKIs and ALK inhibitors.
- 257 patients exhibited other actionable alterations, underscoring the importance of detailed molecular profiling.
- Comprehensive profiling can lead to more effective individualized therapies for NSCLC patients.
