EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset
EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset
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DOI：
10.1038/modpathol.2009.2
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发表时间：
2009-04-01
期刊：
影响因子：
7.5
通讯作者：
Ishikawa, Yuichi
中科院分区：
文献类型：
--
作者：
Inamura, Kentaro;Takeuchi, Kengo;Ishikawa, Yuichi
肺癌的一个子集在染色体2 p内具有小倒位，产生转化融合基因EML 4-ALK（棘皮动物微管相关蛋白样4基因和间变性淋巴瘤激酶基因），其编码活化的酪氨酸激酶。我们先前通过多重逆转录聚合酶链反应检测了363例肺癌标本中EML 4-ALK的存在，确定了11例具有融合基因的腺癌病例。在这项研究中，我们研究了EML 4-ALK阳性病例的临床病理特征，包括EGFR，KRAS和TP 53的突变状态，以及它们是否属于甲状腺转录因子-1（TTF-1）细胞谱系。在11例患者中，4例（36%）年龄小于50岁的EML 4-ALK阳性肺腺癌患者受这些疾病影响，而242例EML 4-ALK阴性肺腺癌患者中有12例（5.0%）受这些疾病影响（P=0.00038）。EML 4-ALK阳性肺腺癌的组织学特征为低分化级别（P=0.0082）和腺泡占优势的结构（P < 0.0001）。此外，EML 4-ALK的存在似乎与EGFR和KRAS突变相互排斥（P=0.00018），而与TP 53突变共存的频率较低（1/11=9.1%），并与不吸烟或轻度吸烟相关（P=0.040），与TTF-1免疫反应性一致。因此，EML 4-ALK阳性肿瘤可能在肺腺癌中形成一种独特的实体，其特征为年轻发病、腺泡组织学、EGFR、KRAS和TP 53无突变或突变罕见以及TTF-1细胞谱系，所有这些均与非吸烟者或轻度吸烟者的患病率一致。
A subset of lung cancers harbors a small inversion within chromosome 2p, giving rise to a transforming fusion gene, EML4-ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene), which encodes an activated tyrosine kinase. We have earlier examined the presence of EML4-ALK by multiplex reverse transcription-polymerase chain reaction in 363 specimens of lung cancer, identifying 11 adenocarcinoma cases featuring the fusion gene. In this study, we clinicopathologically examined the characteristics of the EML4-ALK-positive cases, including the mutation status of EGFR, KRAS, and TP53, and whether they were of thyroid transcription factor-1 (TTF-1) cell lineage or not. Of 11 patients, 4 (36%) with EML4-ALK-positive lung adenocarcinomas who were below 50 years of age were affected by these diseases, as compared with 12 of 242 patients (5.0%) with EML4-ALK-negative lung adenocarcinomas (P=0.00038). EML4-ALK-positive lung adenocarcinomas were characterized by less-differentiated grade (P=0.0082) and acinar-predominant structure (P < 0.0001) in histology. Furthermore, the presence of EML4-ALK appears to be mutually exclusive for EGFR and KRAS mutations (P=0.00018), whereas coexisting with TP53 mutations at a low frequency (1/11=9.1%), and correlating with non- or light smoking (P=0.040), in line with the TTF-1 immunoreactivity. Thus, EML4-ALK-positive tumors may form a distinct entity among lung adenocarcinomas, characterized by young onset, acinar histology, no or rare mutations in EGFR, KRAS, and TP53, and a TTF-1 cell lineage, all in agreement with the prevalence in non- or light smokers.