Clinical Significance and Next-Generation Sequencing of Chinese Pulmonary Sarcomatoid Carcinoma.
Clinical Significance and Next-Generation Sequencing of Chinese Pulmonary Sarcomatoid Carcinoma.
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中国肺肉瘤样癌的临床意义和二代测序
DOI：
10.1038/s41598-017-04296-2
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发表时间：
2017-06-21
影响因子：
4.6
通讯作者：
Chen J
中科院分区：
文献类型：
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作者：
Li X;Wang D;Zhao Q;Ren D;Ren F;Chen G;Liu H;Chen J
肺肉瘤样癌（PSC）是一种预后较差的非小细胞肺癌（nsclc）。本研究对7例PSC患者进行了研究。显微镜下分析7例均为多形性癌亚型。5例（71.4%）完全由恶性肉瘤样元素组成，2例（28.6%）由恶性肉瘤样元素和至少10%的腺癌样元素组成。免疫组化结果显示，7例PSC中波形蛋白和细胞角蛋白（cytokeratin， CK）、细胞角蛋白7 （cytokeratin, CK7）均呈阳性。新一代测序（NGS）共鉴定出136个推测体细胞变异和1个基因融合，其中16个变异被认为是热点突变，包括基因EGFR、EML4-ALK、MET、BRAF、PIK3CA和TP53。在这些热点突变中，一个表达EML4-ALK融合的样本被Ventana IHC进一步证实，一个包含EGFR外显子19缺失的样本也被证实。NGS结果表明，TP53突变经常发生在PSCs中，EML4-ALK融合事件和EGFR外显子缺失也发生在这些罕见的肿瘤中。分子靶向治疗可能是治疗这些罕见肺肿瘤的有效策略。
Pulmonary Sarcomatoid Carcinoma (PSC) constitutes a heterogeneous group of non-small-cell lung carcinomas (NSCLCs) with a poor prognosis. In this study, a group of 7 patients with PSC was studied. Microscope analysis of all 7 cases revealed a pleomorphic carcinoma subtype. Moreover, 5 cases (71.4%) were composed entirely of malignant sarcomatoid-like elements, and 2 cases (28.6%) were composed of malignant sarcomatoid-like elements and at least 10% adenocarcinoma-like elements. Immunohistochemically, the PSC components of all 7 cases were positive for vimentin and cytokeratins, including cytokeratin (CK) and cytokeratin 7 (CK7). Next-Generation Sequencing (NGS) was performed, and a total of 136 putative somatic variants and one gene fusion were identified, of which 16 variants were considered hot spot mutations, including the genes EGFR, EML4-ALK, MET, BRAF, PIK3CA, and TP53. Of these hot spot mutations, one sample expressing an EML4-ALK fusion was further confirmed by Ventana IHC, and one sample containing an EGFR exon 19 deletion was also confirmed. The NGS results imply that TP53 mutations occur often in PSCs and that EML4-ALK fusion events and EGFR exon deletions also occur in these rare tumors. Molecular targeted therapy may be a useful treatment strategy for these rare lung tumors.