High rate of FGFR1 amplifications in brain metastases of squamous and non-squamous lung cancer
High rate of FGFR1 amplifications in brain metastases of squamous and non-squamous lung cancer
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DOI：
10.1016/j.lungcan.2013.10.004
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发表时间：
2014-01-01
期刊：
影响因子：
5.3
通讯作者：
Birner, Peter
中科院分区：
文献类型：
--
作者：
Preusser, Matthias;Berghoff, Anna S.;Birner, Peter
目的：FGFR1扩增在鳞状细胞癌中很常见，在肺腺癌中很少见，但尚未在非小细胞肺癌（NSCLC）脑转移中进行研究。材料和方法：我们对175例NSCLC脑转移瘤和11例匹配的原发肿瘤进行了FGFR1的荧光原位杂交（FISH）和pAKT、PI3K、HIF1a和Ki67的免疫组织化学检测。ALK基因重排状态可从先前的研究中获得。我们对临床、组织病理学和分子数据进行了统计相关性分析。结果：在30/175例（17%）脑转移癌中发现FGFR1扩增；4/21例（19%）鳞癌、20/130例（15.3%）腺癌、2/12例（16.6%）腺鳞癌、4/9例（44.4%）大细胞癌和0/3神经内分泌大细胞癌中发现FGFR1扩增。FGFR1基因状态在9/11可评估病例中原发肿瘤和脑转移瘤中相同。在2/11的病例（1例腺鳞癌和1例大细胞癌）中，FGFR1扩增仅存在于脑转移中，而不存在于原发肿瘤中。此外，我们发现ALK和FGFR1基因扩增状态在脑转移中呈显著正相关（p < 0.001，卡方检验）。FGFR1高水平扩增的患者内脏转移数量显著增加（p < 0.001，卡方检验）。结论：我们的研究结果表明，FGFR1扩增在腺癌的脑转移中富集（其频率是原发肿瘤的5倍），也可能在其他非鳞状癌中富集，但在肺鳞状细胞癌中没有。这些结果可能与NSCLC脑转移的靶向治疗和预防有关。2013爱思唯尔爱尔兰有限公司版权所有。
Objectives: FGFR1 amplifications are common in squamous cell carcinoma and rare in adenocarcinoma of the lung, but have not been investigated in brain metastases of non-small cell lung cancer (NSCLC).Materials and methods: We performed fluorescent in situ hybridization (FISH) for FGFR1 and immunohistochemistry for pAKT, PI3K, HIF1a and Ki67 in 175 NSCLC brain metastases and 11 matched primary tumors. ALK gene rearrangement status was available from a previous study. We performed statistical correlations of clinical, histopathological and molecular data.Results: FGFR1 amplifications were found in a total of 30/175 (17%) brain metastases: 4/21 (19%) squamous cell carcinomas, 20/130 (15.3%) adenocarcinomas, 2/12 (16.6%) adenosquamous carcinomas, 4/9 (44.4%) large cell carcinomas and 0/3 neuroendocrine large cell carcinoma. FGFR1 gene status was identical between primary tumors and brain metastases in 9/11 evaluable cases. In 2/11 cases (1 adenosquamous and 1 large cell carcinoma), FGFR1 amplifications were present only in the brain metastasis and not in the primary tumor. Furthermore, we found a significant positive correlation of ALK and FGFR1 gene amplification status in brain metastases (p < 0.001, Chi square test). Patients with high-level FGFR1 amplifications had significantly higher number of visceral metastases (p < 0.001, Chi square test).Conclusion: Our findings argue for an enrichment of FGFR1 amplifications in brain metastases of adenocarcinomas (where they were 5-fold more frequent than reported for primary tumors) and possibly also of other non-squamous carcinomas, but not in squamous cell carcinomas of the lung. These results may be relevant for targeted therapy and prophylaxis of NSCLC brain metastases. (C) 2013 Elsevier Ireland Ltd. All rights reserved.