title: Detection of ALK rearrangements in malignant pleural effusion cell blocks from patients with advanced non-small cell lung cancer: a comparison of Ventana immunohistochemistry and fluorescence in situ hybridization.
abstract: BACKGROUND
  Surgical resections or tumor biopsies are often not available for patients with late-stage non-small cell lung cancer (NSCLC). Cytological specimens, such as malignant pleural effusion (MPE) cell blocks, are critical for molecular testing. Currently, diagnostic methods to identify anaplastic lymphoma kinase (ALK) rearrangements include fluorescence in situ hybridization (FISH), real-time reverse transcriptase-polymerase chain reaction (RT-PCR), and immunohistochemistry (IHC). In the current study, the authors compared Ventana ALK IHC assays and ALK FISH to detect ALK rearrangements in MPE cell blocks from patients with advanced NSCLC.
  
  
  METHODS
  The ALK IHC assay and ALK FISH were performed on 63 MPE cell blocks. RT-PCR analysis was performed as additional validation in cases in which a discrepancy was observed between the IHC assay and FISH results.
  
  
  RESULTS
  The Ventana ALK IHC assay was found to be informative for all 63 samples, and 8 cases were positive. Fifty-eight cases were interpretable for FISH detection, and 6 were positive. The concordance between IHC and FISH was 100% among the 58 cases. Of the 5 uninterpretable ALK FISH cases, 2 cases and 3 cases, respectively, were ALK IHC positive and negative. One of the 2 ALK IHC-positive cases also demonstrated a positive result in the RT-PCR assay and the patient benefited from crizotinib treatment.
  
  
  CONCLUSIONS
  MPE cell blocks can be used successfully for the detection of ALK rearrangement when tumor tissue is not available. The Ventana ALK IHC assay is an effective screening method for ALK rearrangement in MPE cell blocks from patients with advanced NSCLC, demonstrating high agreement with FISH results.
authors.affiliation: Department of Pathology, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Weiya
authors.initials: W
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tang
authors.forename: Jinnan
authors.initials: J
authors.lastname: Li
authors.forename: Lili
authors.initials: L
authors.lastname: Jiang
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xueying
authors.initials: X
authors.lastname: Su
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D016066:Pleural Effusion, Malignant / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D055752:Small Cell Lung Carcinoma / Q000378:metabolism* / Q000473:pathology
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: Ventana immunohistochemistry (IHC) assay; anaplastic lymphoma kinase (ALK); cell block; fluorescence; fluorescence in situ hybridization (FISH); malignant pleural effusion; non-small cell lung cancer