Epidermal Growth Factor Receptor Mutations in Small Cell Lung Cancer
Epidermal Growth Factor Receptor Mutations in Small Cell Lung Cancer
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DOI：
10.1158/1078-0432.ccr-08-0332
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发表时间：
2008-10-01
影响因子：
11.5
通讯作者：
Yatabe, Yasushi
中科院分区：
文献类型：
--
作者：
Tatematsu, Akiko;Shimizu, Junichi;Yatabe, Yasushi
目的：绝大多数表皮生长因子受体（epidermal growth factor receptor， EGFR）突变发生在肺腺癌中，甚至罕见的其他携带该突变的亚型，如腺鳞癌，也与腺癌组织学有关。根据EGFR突变的腺癌特异性，分析小细胞肺癌（SCLC）的EGFR突变可能为其组织发生提供线索。实验设计：在122例SCLC患者队列中获取EGFR基因的突变状态；所有患者均来自同一研究所。当EGFR发生突变时，也检测其基因拷贝数。结果：5例sclc中检测到EGFR突变（4%）。患者以轻度吸烟者和组织学合并型为主。除了一个肿瘤外，所有肿瘤都有基因扩增。值得注意的是，在三种合并SCLC亚型的肿瘤中，腺癌和SCLC的成分都含有EGFR突变，而基因扩增仅在腺癌成分中检测到。在接受吉非替尼治疗的患者（EGFR突变）中取得了部分缓解。结论：尽管EGFR突变在SCLC中很少见，但轻度吸烟者的SCLC合并腺癌亚型可能存在EGFR突变。对于EGFR突变的患者，EGFR酪氨酸激酶抑制剂可以作为一种治疗选择。在分子发病机制方面，我们认为一些sclc可能是由先前存在的EGFR突变腺癌发展而来的，但考虑到EGFR扩增的不一致分布，其发展可能不是简单的线性。
Purpose: The vast majority of epidermal growth factor receptor (EGFR) mutations occur in lung adenocarcinoma, and even rare cases of other subtypes with this mutation, such as adenosquamous cell carcinoma, are associated with adenocarcinoma histology. According to this adenocarcinoma-specific nature of EGFR mutation, analysis of EGFR mutations with small cell lung cancers (SCLC) may provide a clue to its histogenesis.Experimental Design: The mutational status of the EGFR gene was accessed in a cohort of 122 patients with SCLC; all patients were from a single institute. When the EGFR mutated, its gene copy number was also examined.Results: EGFR mutations were detected in five SCLCs (4%). The patients were mainly in the light smoker and histologic combined subtype. All but one of the tumors harbored gene amplifications. Notably, in three tumors of the combined SCLC subtype, both components of adenocarcinoma and SCLC harbored an EGFR mutation, whereas gene amplification was detected only in the adenocarcinoma component. A partial response was achieved in a patient (with an EGFR mutation) who was treated with gefitinib.Conclusions: Although EGFR mutations are rare in SCLC, a combined subtype of SCLC with adenocarcinoma in light smokers may have a chance of harboring EGFR mutations. For patients with an EGFR mutation, EGFR tyrosine kinase inhibitor can be a treatment option. In terms of molecular pathogenesis, it is suggested that some SCLCs may have developed from pre-existing adenocarcinomas with EGFR mutations, but the development may not be simply linear, taking into consideration the discordant distribution of EGFR amplification.