Data from A Prospective PCR-Based Screening for the <i>EML4-ALK</i> Oncogene in Non–Small Cell Lung Cancer

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<div>Abstract<p><b>Purpose:</b><i>EML4-ALK</i> 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 <i>EML4-ALK</i> is a sensitive and reliable approach.</p><p><b>Experimental Design:</b> We developed a multiplex RT-PCR system to capture <i>ALK</i> fusion transcripts and applied this technique to our prospective, nationwide cohort of non–small cell lung cancer (NSCLC) in Japan.</p><p><b>Results:</b> 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 <i>EML4-ALK</i> and <i>KIF5B-ALK</i> with our RT-PCR system identified <i>EML4-ALK</i> transcripts in 36 samples (4.46%) from 32 individuals (4.24%). The RT-PCR products were detected in specimens including bronchial washing fluid (<i>n</i> = 11), tumor biopsy (<i>n</i> = 8), resected tumor (<i>n</i> = 7), pleural effusion (<i>n</i> = 5), sputum (<i>n</i> = 4), and metastatic lymph node (<i>n</i> = 1). The results of RT-PCR were concordant with those of sensitive immunohistochemistry with ALK antibodies.</p><p><b>Conclusions:</b> Multiplex RT-PCR was confirmed to be a reliable technique for detection of <i>ALK</i> fusion transcripts. We propose that diagnostic tools for <i>EML4-ALK</i> should be selected in a manner dependent on the available specimen types. FISH and sensitive immunohistochemistry should be applied to formalin-fixed, paraffin-embedded tissue, but multiplex RT-PCR is appropriate for other specimen types. <i>Clin Cancer Res; 18(20); 5682–9. ©2012 AACR</i>.</p></div>