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ALK+ lung adenocarcinoma in never smokers and long-term ex-smokers: prevalence and detection by immunohistochemistry and fluorescence in situ hybridization

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Abstract

ALK gene rearrangements are identified in 2–5 % of all non-small cell lung cancer and are more common in lifetime non-smokers with adenocarcinoma, but the prevalence of ALK rearrangements is not as well characterized in long-term ex-smokers (quit >10 years prior to diagnosis). Accurate and timely diagnosis of ALK-rearranged tumors is of clinical importance given the remarkable response to targeted inhibitors. ALK gene rearrangement may be detected by fluorescence in situ hybridization (FISH), and abnormal expression of ALK protein may be detected by immunohistochemistry (IHC), the latter of which is faster and less expensive. The aim of this study is to evaluate the prevalence of ALK rearrangement in non-smokers and long-term ex-smokers with lung adenocarcinoma and to assess the performance of IHC for the detection of ALK+ tumors when compared to FISH. Two hundred fifty-one cases of resected lung adenocarcinoma were retrospectively reviewed, including non-smokers (n = 79) or long-term ex-smokers (n = 172). ALK IHC and ALK FISH were performed on each case. Four cases demonstrated ALK rearrangement by FISH (4/251; 1.6 %). All cases were non-smokers (4/79; 5.1 %), and all were positive for ALK by IHC. No additional cases were considered positive by IHC, and only 26 (10.4 %) cases were considered equivocal using a conservative approach to interpretation, resulting in a sensitivity of 100 % and specificity of 89.5 %. ALK rearrangement was not observed in lung adenocarcinoma arising in long-term ex-smokers, whereas it is seen in up to 5.1 % of lifetime non-smokers. ALK IHC using the 5A4 antibody demonstrates high sensitivity, supporting its use as a screening test.

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Acknowledgments

The authors would like to acknowledge the excellent technical support received from Marissa Goudie, Ossayed Alawor, Makoto Matsueka, and Alison MacDonald and clerical support from Joy Douglas.

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Authors and Affiliations

  1. Department of Pathology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada

    Andrew S Williams, Wenda Greer & Zhaolin Xu

  2. Department of Surgery, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada

    Drew Bethune

  3. Department of Pathology, University Health Network, Toronto, ON, Canada

    Kenneth J Craddock

  4. Department of Community Health and Epidemiology, Dalhousie University, Halifax, NS, Canada

    Gordon Flowerdew

  5. Division of Anatomical Pathology, Queen Elizabeth II Health Sciences Centre, 5788 University Ave. Rm 734C, Halifax, B3H 1V8, NS, Canada

    Zhaolin Xu

Authors
  1. Andrew S Williams
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  2. Wenda Greer
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  3. Drew Bethune
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  4. Kenneth J Craddock
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  5. Gordon Flowerdew
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  6. Zhaolin Xu
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Corresponding author

Correspondence to Zhaolin Xu.

Ethics declarations

This study adhered to scientific and medical standards of ethics and was approved by the regional Research Ethics Board (CDHA-RS/2012-029).

Funding

This study was funded by an Investigator Initiated Research grant from Pfizer (#WS1416261).

Conflict of interest

Dr. Zhaolin Xu is a current member of Pfizer’s National Lung Cancer Medical Advisory Board. Dr. Drew Bethune has been a member of Pfizer’s Medical Advisory Board and AstraZeneca’s Medical Advisory Board. None of the remaining authors declare any potential conflicts of interest.

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Williams, A.S., Greer, W., Bethune, D. et al. ALK+ lung adenocarcinoma in never smokers and long-term ex-smokers: prevalence and detection by immunohistochemistry and fluorescence in situ hybridization. Virchows Arch 469, 533–540 (2016). https://doi.org/10.1007/s00428-016-2005-y

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  • DOI: https://doi.org/10.1007/s00428-016-2005-y

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