Expression profiling of receptor tyrosine kinases in high-grade neuroendocrine carcinoma of the lung: a comparative analysis with adenocarcinoma and squamous cell carcinoma.
Expression profiling of receptor tyrosine kinases in high-grade neuroendocrine carcinoma of the lung: a comparative analysis with adenocarcinoma and squamous cell carcinoma.
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DOI：
10.1007/s00432-015-1989-z
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发表时间：
2015-12
影响因子：
3.6
通讯作者：
Tsuchihara K
中科院分区：
文献类型：
--
作者：
Matsumura Y;Umemura S;Ishii G;Tsuta K;Matsumoto S;Aokage K;Hishida T;Yoshida J;Ohe Y;Suzuki H;Ochiai A;Goto K;Nagai K;Tsuchihara K
随着小细胞肺癌（SCLC）综合基因组分析的进展，需要探索该疾病的新治疗方法。考虑到肿瘤细胞的受体酪氨酸激酶（RTK）与特定抑制剂的药理作用之间的直接联系，我们系统地评估了肺高级别神经内分泌癌[HGNEC，包括SCLC和大细胞神经内分泌癌（LCNEC）]的RTK表达。本研究纳入了 51 名接受手术切除的 LCNEC 和 61 名 SCLC 患者。作为对照组，还分析了 202 名腺癌 (ADC) 患者和 122 名鳞状细胞癌 (SQCC) 患者。所有肿瘤均用 10 个 RTK 的抗体进行染色：c-Kit、EGFR、IGF1R、KDR、ERBB2、FGFR1、c-Met、ALK、RET 和 ROS1。 LCNEC 和 SCLC 患者表现出相似的临床病理特征。 LCNEC 和 SCLC 组之间每个 RTK 的 IHC 评分几乎相同，但与 ADC 或 SQCC 组显着不同。特别是，c-Kit 是唯一在 LCNEC 和 SCLC 中显着表达的 RTK。另一方面，约 20% 的 HGNEC 肿瘤表现出强阳性 RTK 表达，这一比例与 ADC 和 SQCC 肿瘤相似。有趣的是，强阳性 RTK 在单个肿瘤中几乎是相互排斥的。与 ADC 或 SQCC 相比，LCNEC 和 SCLC 的主要 RTK 表达谱相似。在 HGNEC 中观察到的独特的 c-Kit 阳性表明 c-Kit 可能是 HGNEC 中独特的 RTK。本文的在线版本 (doi:10.1007/s00432-015-1989-z) 包含补充材料，可供授权用户使用。
As the comprehensive genomic analysis of small cell lung cancer (SCLC) progresses, novel treatments for this disease need to be explored. With attention to the direct connection between the receptor tyrosine kinases (RTKs) of tumor cells and the pharmacological effects of specific inhibitors, we systematically assessed the RTK expressions of high-grade neuroendocrine carcinomas of the lung [HGNECs, including SCLC and large cell neuroendocrine carcinoma (LCNEC)]. Fifty-one LCNEC and 61 SCLC patients who underwent surgical resection were enrolled in this research. As a control group, 202 patients with adenocarcinomas (ADCs) and 122 patients with squamous cell carcinomas (SQCCs) were also analyzed. All the tumors were stained with antibodies for 10 RTKs: c-Kit, EGFR, IGF1R, KDR, ERBB2, FGFR1, c-Met, ALK, RET, and ROS1. The LCNEC and SCLC patients exhibited similar clinicopathological characteristics. The IHC scores for each RTK were almost equivalent between the LCNEC and SCLC groups, but they were significantly different from those of the ADC or SQCC groups. In particular, c-Kit was the only RTK that was remarkably expressed in both LCNECs and SCLCs. On the other hand, about 20 % of the HGNEC tumors exhibited strongly positive RTK expression, and this rate was similar to those for the ADC and SQCC tumors. Intriguingly, strongly positive RTKs were almost mutually exclusive in individual tumors. Compared with ADC or SQCC, LCNEC and SCLC had similar expression profiles for the major RTKs. The exclusive c-Kit positivity observed among HGNECs suggests that c-Kit might be a distinctive RTK in HGNEC. The online version of this article (doi:10.1007/s00432-015-1989-z) contains supplementary material, which is available to authorized users.