MET FISH-positive status predicts short progression-free survival and overall survival after gefitinib treatment in lung adenocarcinoma with EGFR mutation.
MET FISH-positive status predicts short progression-free survival and overall survival after gefitinib treatment in lung adenocarcinoma with EGFR mutation.
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DOI：
10.1186/s12885-015-1019-1
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发表时间：
2015-02-06
期刊：
影响因子：
3.8
通讯作者：
Gemma A
中科院分区：
文献类型：
--
作者：
Noro R;Seike M;Zou F;Soeno C;Matsuda K;Sugano T;Nishijima N;Matsumoto M;Kitamura K;Kosaihira S;Minegishi Y;Yoshimura A;Kubota K;Gemma A
EGFR基因突变的肺腺癌患者对吉非替尼有显著的反应。然而，最终出现的耐药性限制了平均反应时间。考虑到这一点，我们通过荧光原位杂交（FISH）检测了接受吉非替尼治疗的EGFR基因突变腺癌患者MET基因状态与总生存期（OS）和无进展生存期（PFS）之间的相关性。我们评估了来自接受吉非替尼治疗的腺癌患者的35例EGFR突变肺癌样本。用FISH检测吉非替尼治疗前基因拷贝数（GCNs）和MET基因扩增情况。免疫组化（IHC）检测MET蛋白表达。FISH评估显示，在35份腺癌样本中，10名患者（29%）表现出高多态性（每细胞5个拷贝≦平均MET）， 1名患者（3%）表现出扩增（每细胞2个≦MET基因（红色）/CEP7q（绿色））。免疫组化评价MET蛋白表达不能确定MET高多体状态。11例MET FISH阳性患者的无进展生存期（PFS）和总生存期（OS）明显短于24例MET FISH阴性患者（PFS: p = 0.001, OS: p = 0.03）。MET fish阳性的中位PFS和OS分别为7.6个月和16.8个月，而MET fish阴性的中位PFS和OS分别为15.9个月和33.0个月。单因素分析显示，MET fish阳性是与进展和死亡高风险相关的最显著独立因素（风险比分别为3.83 （p = 0.0008）和2.25 (p = 0.03)）。使用FISH分析检测高多体和MET基因扩增可能有助于预测吉非替尼治疗后肺腺癌患者PFS和OS的缩短。MET基因状态与EGFR-TKI临床结果之间的相关性应通过大规模样本进一步评估。
Lung adenocarcinoma patients with EGFR gene mutations have shown a dramatic response to gefitinib. However, drug resistance eventually emerges which limits the mean duration of response. With that in view, we examined the correlations between MET gene status as assessed by fluorescence in situ hybridization (FISH) with overall survival (OS) and progression-free survival (PFS) in adenocarcinoma patients with EGFR gene mutations who had received gefitinib therapy. We evaluated 35 lung cancer samples with EGFR mutation from adenocarcinoma patients who had received gefitinib. Gene copy numbers (GCNs) and amplification of MET gene before gefitinib therapy was examined by FISH. MET protein expression was also evaluated by immunohistochemistry (IHC). FISH assessment showed that of the 35 adenocarcinoma samples, 10 patients (29%) exhibited high polysomy (5 copies≦mean MET per cell) and 1 patient (3%) exhibited amplification (2≦MET gene (red)/CEP7q (green) per cell). IHC evaluation of MET protein expression could not confirm MET high polysomy status. The Eleven patients with MET FISH positivity had significantly shorter progression-free survival (PFS) and overall survival (OS) than the 24 patients who were MET FISH-negative (PFS: p = 0.001 and OS: p = 0.03). Median PFS and OS with MET FISH-positivity were 7.6 months and 16.8 months, respectively, whereas PFS and OS with MET FISH-negativity were 15.9 months and 33.0 months, respectively. Univariate analysis revealed that MET FISH-positivity was the most significant independent factor associated with a high risk of progression and death (hazard ratio, 3.83 (p = 0.0008) and 2.25 (p = 0.03), respectively). Using FISH analysis to detect high polysomy and amplification of MET gene may be useful in predicting shortened PFS and OS after Gefitinib treatment in lung adenocarcinoma. The correlation between MET gene status and clinical outcomes for EGFR-TKI should be further evaluated using large scale samples.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
51.1
作者：
Mitsudomi, Tetsuya;Morita, Satoshi;Fukuoka, Masahiro
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Fukuoka, Masahiro
影响因子：
11.2
作者：
Nagai, Y;Miyazawa, H;Hagiwara, K
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Hagiwara, K
影响因子：
158.5
作者：
Kobayashi, S;Boggon, TJ;Halmos, B
通讯作者：
Halmos, B
影响因子：
50.5
作者：
Noro, R.;Honda, K.;Yamada, T.
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Yamada, T.