EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers
Kentaro Inamura, Kengo Takeuchi, Yuki Togashi, Kimie Nomura, Hironori Ninomiya, Michiyo Okui, Yukitoshi Satoh, Sakae Okumura, Ken Nakagawa, Manabu Soda, Young Lim Choi, Toshiro Niki, Hiroyuki Mano, Yuichi Ishikawa, Kentaro Inamura, Kengo Takeuchi, Yuki Togashi, Kimie Nomura, Hironori Ninomiya, Michiyo Okui, Yukitoshi Satoh, Sakae Okumura, Ken Nakagawa, Manabu Soda, Young Lim Choi, Toshiro Niki, Hiroyuki Mano, Yuichi Ishikawa
Abstract
Introduction: Very recently, we have found a novel fusion product between the echinoderm microtubule-associated protein-like4 (EML4) and the anaplastic lymphoma kinase (ALK) in non-small cell lung cancers (NSCLCs). Tumors featuring EML4-ALK fusion constitute one subtype of NSCLC that might be highly sensitive to ALK inhibitors. Herein, we present results of a first large scale study of EML4-ALK fusion in lung cancers.
Methods: Using reverse transcription-polymerase chain reaction for EML4-ALK fusion mRNA, we investigated 149 lung adenocarcinomas, 48 squamous cell carcinomas, 3 large-cell neuroendocrine carcinomas, and 21 small-cell carcinomas. For EML4-ALK-positive cancers, we further investigated the presence of ALK fusion proteins by immunohistochemistry.
Results: Five of 149 adenocarcinomas (3.4%) showed EML4-ALK fusion mRNA, this being totally lacking in carcinomas of other types (0/72). In all the fusion-positive cases, ALK fusion protein could be detected in the cytoplasm immunohistochemically. The five fusion cases featured two EML4-ALK variant 1 fusions and three variant 2 fusions. Histologically, both variant 1 cases were mixed type adenocarcinomas, showing papillary with bronchioloalveolar components. Interestingly, all three variant 2 cases were acinar adenocarcinomas, the link being statistically significant (p = 0.00018). None of the five fusion-positive cases demonstrated any mutations of EGFR or KRAS, pointing to a mutually exclusive relationship (p = 0.014). There was no association with smoking habits.
Conclusions: In the present first investigation of EML4-ALK fusion in a large study of lung cancers (5/221), we found an interesting histotype-genotype relationship. Furthermore, we could detect the fusion protein by immunohistochemistry, pointing to possible clinical applications.
Source: PubMed