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Is IHC a reliable stand-alone method for ALK screening?

Answer: YES

  • Immunohistochemistry is an equivalent alternative to FISH for ALK testing.
  • The strength of evidence supporting the use of IHC for ALK testing is adequate and supported by 20 studies.
  • Assays based on 5A4 (Novocastra, Leica Biosystems) and D5F3 (Ventana) have shown clinically acceptable sensitivities and specificities, ranging from 95% to 100%, when compared with ALK FISH results.
  • However, ALK1 antibody (mouse monoclonal anti-human CD246, clone ALK1) typically used to diagnose anaplastic large cell lymphoma is not recommended for ALK rearrangement screening in lung carcinoma.

Lindemann NI et al. Arch Pathol Lab Med. 2018 Mar;142(3):321-346

IASLC ATLAS of ALK and ROS Testing in Lung Cancer, IASLC, Colorado, USA

 

Key Studies in Support of ALK IHC/FISH Concordance

A.J. Van der Wekken et al., Clin Cancer Res. 2017 Aug 1;23(15):4251-4258

Dichotomous ALK-IHC Is a Better Predictor for ALK Inhibition Outcome than Traditional ALK-FISH in Advanced Non-Small Cell Lung Cancer.

T. Mok et al.,

J Thorac Oncol. 2017 Nov; 12(11): S1739-S1740

JCES 01.27 Patients with ALK IHC-Positive/FISH-Negative NSCLC Benefit from ALK TKI Treatment: Response Data from the Global ALEX Trial

L. Jiang et al.,

Am J Surg Pathol. 2016 May;40(5):697-703

Improving Selection Criteria for ALK Inhibitor Therapy in Non–Small Cell Lung Cancer: A Pooled-Data Analysis on Diagnostic Operating Characteristics of Immunohistochemistry.

A.Marchetti et al.,

J Thorac Oncol. 2016 Apr;11(4):487-95

ALK Protein Analysis by IHC Staining after Recent Regulatory Changes: A Comparison of Two Widely Used Approaches, Revision of the Literature, and a New Testing Algorithm.

M. Von Laffert et al.,

J Thorac Oncol. 2014 Nov;9(11):1685-92

Multicenter immunohistochemical ALK-testing of non-small-cell lung cancer shows high concordance after harmonization of techniques and interpretation criteria.

M.W. Wynes et wl.,

J Thorac Oncol. 2014 May;9(5):631-8

An international interpretation study using the ALK IHC antibody D5F3 and a sensitive detection kit demonstrates high concordance between ALK IHC and ALK FISH and between evaluators.

E.C. Minca et al.,

J Mol Diagn. 2013 May;15(3):341-6

ALK status testing in non-small cell lung carcinoma: correlation between ultrasensitive IHC and FISH.

H. Nitta et al.,

J Thorac Oncol. 2013 Aug;8(8):1019-31

New methods for ALK status diagnosis in non-small-cell lung cancer: an improved ALK immunohistochemical assay and a new, Brightfield, dual ALK IHC-in situ hybridization assay.