title: Neuroendocrine phenotype as an acquired resistance mechanism in ALK-rearranged lung adenocarcinoma.
abstract: A 63-year-old caucasian woman, presenting with metastatic primitive lung adenocarcinoma was treated with ALK inhibitor crizotinib treatment for six month. After rapid regression of all known lesions, tumor progression appeared six month later on all the already known lesions. A biopsy of subclavicular lymphadenopathy revealed a carcinoma with neuroendocrine phenotype with both immunohistochemical expression of ALK protein and ALK-rearrangement. It was associated with acquired resistance to crizotinib with ALK-rearrangement but without point mutation or amplification of the ALK gene. We herein report the first case of histological neuroendocrine transformation after ALK inhibitor crizotinib treatment, associated with acquired resistance to crizotinib.
authors.affiliation: Laboratory of Tumor Biology, University Hospital of Bordeaux, F-33604, Pessac, France; EA2406, Histology and Molecular Pathology of Tumors, Univ. Bordeaux, F-33076 Bordeaux, France. Electronic address: charline.caumont@chu-bordeaux.fr.
authors.forename: Charline
authors.initials: C
authors.lastname: Caumont
authors.affiliation: Department of Pneumology, University Hospital of Bordeaux, F-33604, Pessac, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Veillon
authors.affiliation: Laboratory of Tumor Biology, University Hospital of Bordeaux, F-33604, Pessac, France; EA2406, Histology and Molecular Pathology of Tumors, Univ. Bordeaux, F-33076 Bordeaux, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Gros
authors.affiliation: Laboratory of Tumor Biology, University Hospital of Bordeaux, F-33604, Pessac, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Laharanne
authors.affiliation: Department of Pathology, University Hospital of Bordeaux, F-33604, Pessac, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Bégueret
authors.affiliation: Laboratory of Tumor Biology, University Hospital of Bordeaux, F-33604, Pessac, France; EA2406, Histology and Molecular Pathology of Tumors, Univ. Bordeaux, F-33076 Bordeaux, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Merlio
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000077548:Anaplastic Lymphoma Kinase; D002968:Clavicle / Q000473:pathology; D000077547:Crizotinib; D019008:Drug Resistance, Neoplasm; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK; Adenocarcinoma; Crizotinib; Neuroendocrine; Non-small cell lung carcinoma