INSERM U935, Poitiers University, Poitiers, France.
Cancer Med. 2013 Jun;2(3):296-304. doi: 10.1002/cam4.82. Epub 2013 Apr 23.
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.
本研究旨在确定非小细胞肺癌脑转移瘤（BM-NSCLC）中表皮生长因子受体（EGFR）、KRAS、BRAF 和 HER-2 突变的频率。共纳入 77 例 BM-NSCLC 样本，并同时研究了 19 例来自乳腺癌、肾和结直肠癌的 BM 样本作为对照。这些样本均来自于 2008 年至 2011 年在法国普瓦捷和尼斯大学医院就诊的患者。BM-NSCLC 中 EGFR、KRAS、BRAF 和 HER-2 突变的频率分别为 2.6%、38.5%、0%和 0%。KRAS 突变在女性和年轻患者中的发生率明显更高（P<0.05）。在乳腺癌或肾癌的 BM 中未发现这四个基因的突变。然而，在 6 例来自结直肠癌的 BM 中，我们发现 3 例存在 KRAS 突变，2 例存在 BRAF 突变。本研究是迄今为止针对 BM-NSCLC 中遗传改变进行的最大规模分析。我们的结果表明，BM-NSCLC 中 EGFR 突变的频率较低，而 KRAS 突变与原发性 NSCLC 中的频率相当。这些结果提出了 NSCLC 细胞脑转移潜能与突变模式的可变性问题。
