Could Detailed Alk-Status Reporting Help Better Understand Therapy Response to Crizotinib?

Maximilian von Laffert, Florian Alius, Ergin Kilic, Manuela Gerhold, Dido Lenze, Albrecht Stenzinger, Bettina Temmesfeld Wollbrück, Manfred Dietel, Norbert Suttorp, Jens-Carsten Rückert, Jens Neudecker, Mahmoud Ismail, Nikolaj Frost, Michael Hummel, Antje Tessmer and Frederick Klauschen

Department of Pathology, Humboldt University Berlin, Germany
Department of Internal Medicine/Infectious Diseases, Charité, Medical School, Germany
Department of Pathology, University of Heidelberg, Germany
Department of General, Visceral, Vascular and Thoracic Surgery, Universitatsmedizin Berlin, Germany

^*Correspondance to: Frederick Klauschen 

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Abstract:

Anaplastic lymphoma kinase (ALK) rearrangements have been found to be actionable mutations in non-small cell lung cancer (NSCLC). ALK-tyrosine kinase inhibitors (TKI) showed very promising therapy response rates and extended progression free survival. We report on three patients, each with an unequivocal ALK-positive status on the protein and genetic level. Two patients show a good response to ALK-inhibition whereas one patient is a non-responder. The latter displayed an unequivocal ALK-positive pattern by immunohistochemistry (IHC) and FISH (fluorescence insitu hybridization), the latter with an additional copy number gain (CNG) of the 3´signal. To date, CNG-patterns were reported as contributors to acquired crizotinib resistance only. Despite the anecdotal character, our report might suggest that this kind of ALK-FISH pattern also plays a role in the context of intrinsic resistance.

Keywords:

Anaplastic lymphoma kinase; Non-small cell lung cancer; Fluorescence in situ hybridization; Immunohistochemistry; Intrinsic resistance; Acquired resistance

Cite the Article:

von Laffert M, Alius F, Kilic E, Gerhold M, Lenze D, Stenzinger A, et al. Could Detailed Alk-Status Reporting Help Better Understand Therapy Response to Crizotinib? Clin Oncol. 2016; 1: 1152.