title: Anaplastic lymphoma kinase gene rearrangements in cytological samples of non-small cell lung cancer: comparison with histological assessment.
abstract: BACKGROUND
  Anaplastic lymphoma kinase (ALK) gene rearrangements are detected in approximately 5% of cases of non-small cell lung cancer (NSCLC). Patients who are positive for ALK rearrangements may be successfully treated with the ALK inhibitor crizotinib. Because advanced-stage lung cancers are not suitable for surgical resection, approximately 70% of patients are diagnosed via preoperative specimens. In the current study, the authors evaluated the suitability of stained cytologic direct smears and cell blocks for fluorescence in situ hybridization (FISH) to determine ALK status compared with small biopsies.
  
  
  METHODS
  A total of 493 consecutive patients with NSCLC were analyzed by FISH for ALK gene rearrangements. The analyzed sample comprised 180 cytological samples, 94 direct smears, 86 cell blocks, and 313 preoperative small biopsies. Moreover, in the same series, 426 patients and 369 patients, respectively, were evaluated for epidermal growth factor receptor and KRAS mutations, respectively.
  
  
  RESULTS
  Of the total of 493 patients, 18 patients who were positive for a gene rearrangement (4.4%) demonstrated ALK FISH rearrangements, whereas 387 patients (95.6%) were negative. All other cases were classified as inadequate (7.7%) and insufficient (10.1%). A strong statistical association was found between the cytology and the small biopsy with respect to ALK rearrangements (P=.0048). Fifty-three patients (12.4%) demonstrated an epidermal growth factor receptor mutation, whereas 90 patients (24.4%) were found to have KRAS mutations. None of these patients presented with ALK gene rearrangements.
  
  
  CONCLUSIONS
  ALK gene rearrangements may be easily detected in cytological samples and particularly in direct smears, thereby yielding important improvements in the diagnostic approach to patients with advanced NSCLC. Cytological samples may be useful for ALK analysis when insufficient material is available in cell blocks or small biopsies.
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Area, Unit of Pathological Anatomy, University of Pisa, Pisa, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Proietti
authors.forename: Greta
authors.initials: G
authors.lastname: Alì
authors.forename: Serena
authors.initials: S
authors.lastname: Pelliccioni
authors.forename: Cristiana
authors.initials: C
authors.lastname: Lupi
authors.forename: Elisa
authors.initials: E
authors.lastname: Sensi
authors.forename: Laura
authors.initials: L
authors.lastname: Boldrini
authors.forename: Adele
authors.initials: A
authors.lastname: Servadio
authors.forename: Antonio
authors.initials: A
authors.lastname: Chella
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ribechini
authors.forename: Federico
authors.initials: F
authors.lastname: Cappuzzo
authors.forename: Mario
authors.initials: M
authors.lastname: Miccoli
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fontanini
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D003581:Cytodiagnosis; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: anaplastic lymphoma kinase (ALK); cytology; fluorescence in situ hybridization (FISH); histology; lung cancer