EGFR, KRAS, BRAF, and HER‐2 molecular status in brain metastases from 77 NSCLC patients

• Published in: Cancer medicine (Malden, MA) Vol. 2; no. 3; pp. 296 - 304
• Main Authors: Villalva, Claire, Duranton‐Tanneur, Valérie, Guilloteau, Karline, Burel‐Vandenbos, Fanny, Wager, Michel, Doyen, Jérôme, Levillain, Pierre Marie, Fontaine, Denys, Blons, Hélène, Pedeutour, Florence, Karayan‐Tapon, Lucie
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-06-2013; Blackwell Publishing Ltd
• Subjects: Adult; Aged; Aged, 80 and over; Amino acids; BRAF; Brain cancer; brain metastases; Brain Neoplasms - genetics; Brain Neoplasms - secondary; Breast; Cancer Biology; Cancer therapies; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Deoxyribonucleic acid; DNA; Epidermal growth factor; epidermal growth factor receptor; Epidermal growth factor receptors; Female; Genes, ras; Genetic analysis; HER‐2; Humans; Kidneys; Kinases; KRAS; Lung cancer; Lung carcinoma; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical prognosis; Melanoma; Metastases; Metastasis; Middle Aged; Mutation; Non-small cell lung carcinoma; non‐small cell lung cancer; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; Receptor, Epidermal Growth Factor - genetics; Receptor, ErbB-2 - genetics; Small cell lung carcinoma; Software; Tumors; France; non-small cell lung cancer; BRAF; KRAS; HER-2; brain metastases; epidermal growth factor receptor
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.82

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.
This study of EGFR, KRAS, BRAF and HER‐2 mutational status in 77 brain metastases from non‐small cell lung cancer (NSCLC) reveals a low frequency of EGFR mutations whereas KRAS mutations are as frequent as in primitive NSCLC. These results raise the question of the variability of brain metastatic potential of NSCLC cells in relationship to mutation patterns.