title: ALK and ROS1 rearrangements tested by fluorescence in situ hybridization in cytological smears from advanced non-small cell lung cancer patients.
abstract: BACKGROUND
  The identification of ALK and ROS1 rearrangements and the availability of an effective target therapy, such as crizotinib, represent a new option in the treatment of advanced non-small cell lung cancer (NSCLC) patients. In light of recent advances in non-invasive diagnostic procedures, we aimed to demonstrate that direct cytological smears are suitable for assessing ALK and ROS1 rearrangements in patients with NSCLC.
  
  
  METHODS
  Fifty-five patients with a cytological diagnosis of lung adenocarcinoma (ADC) were evaluated for ALK rearrangements by fluorescence in situ hybridization (FISH) and 12 patients for ROS1 FISH rearrangements. Seventeen of the 55 cytological samples tested for ALK were obtained from the primary tumor and 38 from metastatic lesions. Ten of 12 samples evaluated for ROS1 were obtained from metastatic sites and two from the primary tumor.
  
  
  RESULTS
  ALK FISH was successful in 49/55 (89%) cytological ADC samples and ROS1 FISH in all 12 cytological samples. ALK rearrangements were found in 3/13 (23%) primary tumors and 7/36 (19%) metastatic sites. ROS1 rearrangements were found in one of the two primary tumors and in two of the 10 metastases. Two of the three rearranged cases were tested on cytology after knowing that they were rearranged on histology in order to increase representativeness of ROS1 rearranged cases in this study.
  
  
  CONCLUSIONS
  Whenever cytology represents the only available material for diagnosis and biological characterization of NSCLC, minimally invasive procedures may provide an additional important source of cellular material for FISH assessment of ALK and ROS1 rearrangements.
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bozzetti
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Nizzoli
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tiseo
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Squadrilli
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences, University Hospital of Parma, Parma, Italy.
authors.forename: Costanza
authors.initials: C
authors.lastname: Lagrasta
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Buti
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: Donatello
authors.initials: D
authors.lastname: Gasparro
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Zanoni
authors.affiliation: Pneumology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Majori
authors.affiliation: Radiology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: De Filippo
authors.affiliation: Department of Medical Oncology, Careggi Hospital of Firenze, Firenze, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mazzoni
authors.affiliation: Cytopathology Unit, Cancer Prevention and Research Institute, Firenze, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Maddau
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Naldi
authors.affiliation: Department of Clinical and Experimental Medicine, Haematology and Bone Marrow Transplantation Unit, University Hospital of Parma, Parma, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sammarelli
authors.affiliation: Clinical and Experimental Medicine, University Hospital of Parma, Parma, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Frati
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Pinto
authors.affiliation: Medical Oncology Unit, S.Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ardizzoni
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000601:surgery; D003581:Cytodiagnosis / Q000379:methods; D005260:Female; D015321:Gene Rearrangement / Q000502:physiology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*
chemical_list: D011518:Proto-Oncogene Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK; FISH; ROS1; cytology; non-small cell lung cancer