title: A year of anaplastic large cell kinase testing for lung carcinoma: pathological and technical perspectives.
abstract: BACKGROUND
  An in-frame fusion protein between echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic large cell kinase (ALK) genes is seen in some non-small cell lung cancer (NSCLC). EML4-ALK demonstrates constitutive kinase activity. These ALK-positive lung carcinomas have been shown to respond to ALK kinase inhibitors. ALK gene rearrangement is commonly detected using fluorescent in situ hybridization (FISH).
  
  
  OBJECTIVE
  To study the pathological features of ALK positive and negative NSCLC and evaluate the causes of uninterpretable FISH results.
  
  
  METHODS
  This is a retrospective, observational study. The molecular pathology records of patients on whom test for ALK had been performed in a period of 1 year (February 2012 to February 2013) were accessioned. A total 224 cases were identified. Histological features were reviewed. The in situ hybridization was performed using Vysis ALK Dual Color Break Apart Rearrangement Probe (Abbott Molecular Inc.). Signal interpretation under the fluorescent microscope was performed in accordance with College of American Pathologists guidelines.
  
  
  RESULTS
  Five patients showed ALK gene rearrangement, 182 were negative and 37 cases were uninterpretable. Five patients with ALK gene rearrangement had a mean age of 48 years and the male to female ratio was 2:3. In the ALK negative cases, the mean age was 54 years and male to female ratio was 3.2:1. Histologically, amongst the rearranged cases, three showed solid pattern, one showed acinar and one showed acinar with signet ring cells on histology.
  
  
  CONCLUSIONS
  The percentage of ALK gene rearrangement was 2.7% (excluding the uninterpretable cases). These ALK positive patients were relatively younger than ALK negative patients. Solid pattern on histology was associated with ALK positivity. In a quarter of the uninterpretable results, the material submitted was fixed and processed outside.
authors: Department of Pathology, Tata Memorial Hospital and Advanced Centre for Training Research and Education, Mumbai, Maharashtra, India. saraldesai@gmail.com
authors: S S
authors: SS
authors: Desai
authors: A S
authors: AS
authors: Shah
authors: K
authors: K
authors: Prabhash
authors: N A
authors: NA
authors: Jambhekar
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000302:isolation & purification; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D012189:Retrospective Studies
chemical_list: C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors