EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset

被引:336
作者
Inamura, Kentaro [1 ]
Takeuchi, Kengo [1 ]
Togashi, Yuki [1 ]
Hatano, Satoko [1 ]
Ninomiya, Hironori [1 ]
Motoi, Noriko [1 ]
Mun, Ming-yon [2 ]
Sakao, Yukinori [2 ]
Okumura, Sakae [2 ]
Nakagawa, Ken [2 ]
Soda, Manabu [3 ]
Choi, Young Lim [3 ]
Mano, Hiroyuki [3 ]
Ishikawa, Yuichi [1 ]
机构
[1] Japanese Fdn Canc Res, Div Pathol, Inst Canc, Koto Ku, Tokyo 1358550, Japan
[2] Canc Inst Hosp, JFCR, Dept Thorac Surg, Koto Ku, Tokyo, Japan
[3] Jichi Med Univ, Div Funct Genom, Shimotsuke, Tochigi, Japan
基金
日本学术振兴会;
关键词
lung cancer; EML4-ALK; gene mutation; TTF-1; histology; RECEPTOR GENE-MUTATIONS; P53; MUTATIONS; FUSION GENE; ADENOCARCINOMAS; GEFITINIB; IDENTIFICATION; FEATURES; SMOKING;
D O I
10.1038/modpathol.2009.2
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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.
引用
收藏
页码:508 / 515
页数:8
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