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Published on: February 8, 2017
EGFR, KRAS, BRAF, and HER-2 molecular status in brain metastases from 77 NSCLC patients
Claire Villalva1, Valérie Duranton-Tanneur, Karline Guilloteau
1INSERM U935, Poitiers University, Poitiers, France.
Abstract:
The aim of this study was to determine the frequency of EGFR, KRAS, BRAF, and HER-2 mutations in brain metastases from non-small cell lung carcinomas (BM-NSCLC). A total of 77 samples of BM-NSCLC were included and 19 samples of BM from breast, kidney, and colorectal tumors were also studied as controls. These samples were collected from patients followed between 2008 and 2011 at Poitiers and Nice University Hospitals in France. The frequencies of EGFR, KRAS, BRAF, and HER-2 mutations in BM-NSCLC were 2.6, 38.5, 0, and 0% respectively. The incidence of KRAS mutation was significantly higher in female and younger patients (P < 0.05). No mutations of the four genes were found in BM from breast or kidney. However, among six BM from colorectal tumors, we identified KRAS mutations in three cases and BRAF mutations in two other cases. This study is the largest analysis on genetic alterations in BM-NSCLC performed to date. Our results suggest a low frequency of EGFR mutations in BM-NSCLC whereas KRAS mutations are as frequent in BM-NSCLC as in primitive NSCLC. These results raise the question of the variability of the brain metastatic potential of NSCLC cells in relation to the mutation pattern.
Insights
This study analyzed mutations in brain metastases from non-small cell lung cancer (NSCLC), finding KRAS mutations were common, similar to primary NSCLC. EGFR mutations were infrequent in these brain metastases.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Brain metastases are a significant complication of non-small cell lung cancer (NSCLC).
- Understanding the genetic landscape of NSCLC brain metastases (BM-NSCLC) is crucial for targeted therapy.
- Previous studies have limited data on mutation frequencies in BM-NSCLC.
Purpose of the Study:
- To determine the mutation frequencies of EGFR, KRAS, BRAF, and HER-2 in BM-NSCLC.
- To compare mutation patterns in BM-NSCLC with those in primary NSCLC and brain metastases from other cancers.
- To investigate potential correlations between KRAS mutations and patient demographics.
Main Methods:
- Analysis of 77 BM-NSCLC samples and 19 control brain metastasis samples (breast, kidney, colorectal).
- Genotyping for EGFR, KRAS, BRAF, and HER-2 mutations.
- Statistical analysis to assess mutation incidence and patient characteristics.
Main Results:
- EGFR, BRAF, and HER-2 mutations were rare (2.6%, 0%, 0%) in BM-NSCLC.
- KRAS mutations were found in 38.5% of BM-NSCLC, a frequency comparable to primary NSCLC.
- KRAS mutations showed a higher incidence in younger and female patients.
- No mutations were detected in breast or kidney BM; KRAS and BRAF mutations were found in colorectal BM.
Conclusions:
- EGFR mutations are infrequent in BM-NSCLC.
- KRAS mutations are common in BM-NSCLC, suggesting similar oncogenic drivers as primary NSCLC.
- The findings highlight the importance of molecular profiling of BM-NSCLC to guide treatment decisions and raise questions about the metastatic potential related to mutation patterns.
