Virchows Archiv

, Volume 463, Issue 4, pp 583–591

Immunohistochemistry reliably detects ALK rearrangements in patients with advanced non-small-cell lung cancer

  • Xiao-Hong Han
  • Ning-Ning Zhang
  • Li Ma
  • Dong-Mei Lin
  • Xue-Zhi Hao
  • Yu-Tao Liu
  • Lin Wang
  • Peng Liu
  • Zheng Yuan
  • Dan Li
  • Hua Lin
  • Yan Sun
  • Yuan-Kai Shi
Original Article

DOI: 10.1007/s00428-013-1472-7

Cite this article as:
Han, XH., Zhang, NN., Ma, L. et al. Virchows Arch (2013) 463: 583. doi:10.1007/s00428-013-1472-7

Abstract

Accurate determination of anaplastic lymphoma kinase (ALK) rearrangements is critical in identifying ALK-positive patients for targeted therapy in non-small-cell lung cancer (NSCLC). Fluorescence in situ hybridization (FISH) is the current standard method to detect ALK rearrangements but is technically challenging and costly. We compared optimised immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization techniques in this study of 139 samples of advanced NSCLC with non-squamous histology. ALK alteration was found in 32.6 % (43/132) of patients by FISH, 32.9 % (45/137) of patients by IHC and 27.9 % (34/122) of samples by qRT-PCR (concordance rate of 96.9 % between FISH and IHC, 95.7 % between FISH and qRT-PCR, P < 0.001). IHC sensitivity and specificity were 97.7 % and 96.6 %, respectively, while the sensitivity and specificity of qRT-PCR were 89.2 % and 98.7 %, respectively. ALK rearrangements were more common in young patients (P = 0.007), non-smokers or light smokers (P = 0.008) and adenocarcinoma histology, especially with signet ring cell features (P < 0.001). Optimised IHC could be a useful method in screening ALK rearrangements in clinical practice with qRT-PCR as an alternative diagnostic tool to clarify specific ALK variants.

Keywords

Non-small-cell lung cancerAnaplastic lymphoma kinaseEML4-ALKFluorescence in situ hybridizationImmunohistochemistryqRT-PCR

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Xiao-Hong Han
    • 1
  • Ning-Ning Zhang
    • 1
  • Li Ma
    • 1
  • Dong-Mei Lin
    • 2
  • Xue-Zhi Hao
    • 1
  • Yu-Tao Liu
    • 1
  • Lin Wang
    • 1
  • Peng Liu
    • 1
  • Zheng Yuan
    • 2
  • Dan Li
    • 1
  • Hua Lin
    • 3
  • Yan Sun
    • 1
  • Yuan-Kai Shi
    • 1
  1. 1.Department of Medical OncologyCancer Institute/Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted DrugsBeijingChina
  2. 2.Department of PathologyCancer Institute/Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  3. 3.Department of Medical RecordCancer Institute/Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina