Expression profiling and identification of potential molecular targets for therapy in pulmonary large-cell neuroendocrine carcinoma
Expression profiling and identification of potential molecular targets for therapy in pulmonary large-cell neuroendocrine carcinoma
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DOI：
10.3892/etm.2011.343
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发表时间：
2011-11-01
影响因子：
2.7
通讯作者：
Satoh, Yukitoshi
中科院分区：
文献类型：
--
作者：
Iyoda, Akira;Travis, William D.;Satoh, Yukitoshi
肺大细胞神经内分泌癌（LCNEC）患者的预后极差，尚未建立最佳治疗方法。最近有报道，分子靶向治疗，如表皮生长因子受体（EGFR）的酪氨酸激酶抑制剂，是有效的肺癌患者。为了改善LCNEC患者的预后，我们分析了LCNEC中已知分子靶点的基因表达、基因突变和免疫组化（IHC）表达，并将其表达与肺腺癌（AC）的表达进行了比较。分析了13例原发性LCNEC和14例AC患者。我们评估了c-KIT、人表皮生长因子受体2型（HER 2）和血管内皮生长因子（VEGF）的IHC表达，EGFR、K-ras和c-kit的基因突变，以及EGFR的荧光原位杂交基因表达。在LCNEC病例中，c-KIT、HER 2和VEGF的IHC表达分别为76.9%、30.8%和100%。LCNEC和AC病例之间c-KIT和HER 2的IHC表达存在显著差异。2例LCNEC有HER 2过表达，AC组EGFR基因突变频率较高，LCNEC组仅发现单一EGFR突变（外显子18）。尽管LCNEC中c-KIT表达率较高，但未发现c-kit基因突变，提示抗VEGF、抗c-KIT和抗HER 2靶向药物在LCNEC治疗中可能发挥作用。
The prognosis for patients with large-cell neuroendocrine carcinoma (LCNEC) of the lung is extremely poor, and an optimal treatment has not yet been established. It has been recently reported that molecular-targeted therapies, such as tyrosine kinase inhibitors for epidermal growth factor receptor (EGFR), are effective in patients with lung carcinoma. In efforts to improve the prognosis of patients with LCNEC, we analyzed gene expression, gene mutations and immunohistochemical (IHC) expression of known molecular targets in LCNECs, and compared the expression to that of lung adenocarcinomas (ACs). Thirteen patients with primary LCNEC and 14 patients with AC were analyzed. We evaluated IHC expression for c-KIT, human epidermal growth factor receptor type 2 (HER2) and vascular endothelial growth factor (VEGF), gene mutations for EGFR, K-ras and c-kit, and gene expression using fluorescence in situ hybridization for EGFR. In cases with LCNEC, the IHC expression of c-KIT, HER2 and VEGF was 76.9, 30.8 and 100%, respectively. There was a significant difference in the IHC expression of c-KIT and HER2 between the LCNEC and AC cases. Two cases of LCNEC had overexpression of HER2, and the frequency of EGFR gene mutations was higher in the the AC group, with only a single EGFR mutation (exon 18) identified in the LCNEC group. Although LCNEC had a higher rate of expression of c-KIT by IHC, no c-kit gene mutations were found. These findings suggest a potential role for anti-VEGF-, anti-c-KIT- and possibly anti-HER2-targeted agents in the treatment of LCNEC.