A prospective PCR-based screening for the EML4-ALK oncogene in non-small cell lung cancer

Manabu Soda, Kazutoshi Isobe, Akira Inoue, Makoto Maemondo, Satoshi Oizumi, Yuka Fujita, Akihiko Gemma, Yoshihiro Yamashita, Toshihide Ueno, Kengo Takeuchi, Young Lim Choi, Hitoshi Miyazawa, Tomoaki Tanaka, Koichi Hagiwara, Hiroyuki Mano

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Abstract

Purpose: EML4-ALK is a lung cancer oncogene, and ALK inhibitors show marked therapeutic efficacy for tumors harboring this fusion gene. It remains unsettled, however, how the fusion gene should be detected in specimens other than formalin-fixed, paraffin-embedded tissue. We here tested whether reverse transcription PCR (RT-PCR)-based detection of EML4-ALK is a sensitive and reliable approach. Experimental Design: We developed a multiplex RT-PCR system to capture ALK fusion transcripts and applied this technique to our prospective, nationwide cohort of non-small cell lung cancer (NSCLC) in Japan. Results: During February to December 2009, we collected 916 specimens from 853 patients, quality filtering of which yielded 808 specimens of primary NSCLC from 754 individuals. Screening for EML4-ALK and KIF5B-ALK with our RT-PCR system identified EML4-ALK transcripts in 36 samples (4.46%) from 32 individuals (4.24%). The RT-PCR products were detected in specimens including bronchial washing fluid (n = 11), tumor biopsy (n = 8), resected tumor (n = 7), pleural effusion (n = 5), sputum (n = 4), and metastatic lymph node (n = 1). The results of RT-PCR were concordant with those of sensitive immunohistochemistry with ALK antibodies. Conclusions: Multiplex RT-PCR was confirmed to be a reliable technique for detection of ALK fusion transcripts. We propose that diagnostic tools for EML4-ALK should be selected in a manner dependent on the available specimen types. FISH and sensitive immunohistochemistry should be applied to formalinfixed, paraffin-embedded tissue, but multiplex RT-PCR is appropriate for other specimen types.

Original languageEnglish
Pages (from-to)5682-5689
Number of pages8
JournalClinical Cancer Research
Volume18
Issue number20
DOIs
Publication statusPublished - 2012 Oct 15

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Soda, M., Isobe, K., Inoue, A., Maemondo, M., Oizumi, S., Fujita, Y., Gemma, A., Yamashita, Y., Ueno, T., Takeuchi, K., Choi, Y. L., Miyazawa, H., Tanaka, T., Hagiwara, K., & Mano, H. (2012). A prospective PCR-based screening for the EML4-ALK oncogene in non-small cell lung cancer. Clinical Cancer Research, 18(20), 5682-5689. https://doi.org/10.1158/1078-0432.CCR-11-2947