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Published on: August 11, 2017
Epidermal growth factor receptor gene in primary tumor and metastatic sites from non-small cell lung cancer
Lorenzo Daniele1, Paola Cassoni, Elisa Bacillo
1Department of Biomedical Sciences and Human Oncology, University of Turin, Turin, Italy. lorenzo.daniele@unito.it
Introduction:
The majority of patients with non-small cell lung cancer (NSCLC) develop distant metastases. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are capable of reducing brain and adrenal metastases. However, the EGFR status may be discordant between primary NSCLC and the corresponding metastases.
Methods:
Using fluorescence in situ hybridization (FISH) analysis, the EGFR gene status was evaluated in a series of 38 cerebral or adrenal metastases collected from two institutions and in the corresponding primary tumors. Also, EGFR mutational analysis was performed using direct sequencing on the cerebral metastases.
Results:
EGFR FISH was positive in 28% of the primary tumors and in 45% of the metastases (p < 0.05). Among the seven cases FISH-positive at the metastatic site but negative in the primary tumor, six were brain metastases, and one was an adrenal metastasis; all were polysomic for chromosome 7, none were amplified. No EGFR mutations have been found in the cerebral metastases.
Conclusion:
Because the molecular asset of EGFR may change during the metastatic progression of NSCLC to brain (but not to adrenal), the selection of patients with brain metastasis for specific targeted therapies by EGFR FISH analysis should be performed on metastatic lesions rather than on their corresponding primary tumors.
Insights
Epidermal growth factor receptor (EGFR) status can change in non-small cell lung cancer (NSCLC) metastases. Testing EGFR in brain metastases, not primary tumors, is crucial for targeted therapy selection.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Most non-small cell lung cancer (NSCLC) patients develop distant metastases.
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors show efficacy against brain and adrenal metastases.
- EGFR status can differ between primary NSCLC and its metastases.
Purpose of the Study:
- To investigate discordance in EGFR gene status between primary NSCLC and metastatic lesions.
- To determine the optimal site for EGFR testing in NSCLC patients with brain or adrenal metastases.
Main Methods:
- Fluorescence in situ hybridization (FISH) was used to assess EGFR gene status in 38 primary NSCLC tumors and their corresponding cerebral or adrenal metastases.
- Direct sequencing was performed for EGFR mutational analysis on cerebral metastases.
Main Results:
- EGFR FISH positivity was higher in metastases (45%) than in primary tumors (28%).
- Six of seven cases with EGFR FISH-positive metastases but FISH-negative primary tumors were brain metastases.
- No EGFR mutations were detected in the analyzed cerebral metastases.
Conclusions:
- EGFR molecular profile can change during NSCLC metastatic progression to the brain.
- EGFR FISH analysis for targeted therapy selection in NSCLC brain metastases should be performed on metastatic lesions.
- EGFR status in adrenal metastases did not show the same discordance as in brain metastases.
