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Combination of morphological feature analysis and immunohistochemistry is useful for screening of EML4-ALK-positive lung adenocarcinoma
  1. Ryu Jokoji1,
  2. Takashi Yamasaki1,
  3. Seigo Minami2,
  4. Kiyoshi Komuta2,
  5. Yasushi Sakamaki3,
  6. Kengo Takeuchi4,
  7. Masahiko Tsujimoto1
  1. 1Department of Pathology, Osaka Police Hospital, Tennouji-ku, Osaka, Japan
  2. 2Department of Respiratory Medicine, Osaka Police Hospital, Tennouji-ku, Osaka, Japan
  3. 3Department of Chest Surgery, Osaka Police Hospital, Tennouji-ku, Osaka, Japan
  4. 4Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Ariake, Koto-ku, Tokyo, Japan
  1. Correspondence to Masahiko Tsujimoto, Department of Pathology, Osaka Police Hospital, 10–31 Kitayama-cho, Tennouji-ku, Osaka 543-0035, Japan; patho{at}


Background A subset of lung cancers harbours the fusion gene echinoderm microtubule-associated protein-like-4–anaplastic lymphoma kinase (EML4-ALK). Recently, immunohistochemistry for ALK has shown sensitivity for the detection of EML4-ALK-positive lung adenocarcinoma almost equal to that of the fluorescence in situ hybridisation (FISH) assay.

Aims To study the clinicopathological features of EML4-ALK-positive lung adenocarcinoma in a large number of surgically resected samples using immunohistochemistry, in order to establish a useful screening method for EML4-ALK-positive lung adenocarcinoma.

Methods Immunohistochemistry for ALK was used to screen for EML4-ALK-positive lung adenocarcinomas in 254 cases of surgically resected samples.

Results EML4-ALK-positive cases were detected in 3.1% of lung adenocarcinomas (8/254). EML4-ALK-positive lung adenocarcinomas showed significant associations with intra- and/or extra-cytoplasmic mucin (p=0.0001), and cribriform pattern with excessive extracytoplasmic mucin (p<0.0001). Signet-ring cell appearance alone lacked significance (p=0.149).

Conclusion EML4-ALK-positive lung adenocarcinoma has a tendency to express a characteristic morphological pattern. The combined use of morphological feature analysis and immunohistochemistry may be a useful and cost effective screening method for EML4-ALK lung adenocarcinoma.

  • Lung cancer
  • EML4-ALK
  • immunohistochemistory
  • morphology
  • mucin

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  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the ethics committee of Osaka Police Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.