Reliable Screening Tool Found for Lung Cancer Subtype

The identification of an effective therapy for ALK-positive NSCLC places great emphasis on rapid, accurate, and cost-effective way to find patients with this subtype of lung cancer, although the complex fluorescence in situ hybridization (FISH) is the current standard method to detect ALK rearrangement.

The FISH technology is not readily available as a routine method of pathology practice in most laboratories because it is time consuming and requires advanced technical and professional expertise. In contrast, IHC is relatively inexpensive, faster, and is perfectly adapted for routine practice by academics and most community hospitals.

Scientists led by those at University of British Columbia (Vancouver, BC, Canada) screened 377 stage I or II NSCLC cases in a tissue microarray by FISH and IHC (Leica Microsystems; Wetzlar, Germany) or using the N-Histofine ALK detection kit (Nichirei Biosciences; Tokyo, Japan) and monoclonal antibodies. IHC was scored as 0, 1+, 2+, or 3+. Possible positive or positive cases were further analyzed by IHC and FISH on whole sections.

Tissue microarray results were available on 377 cases by IHC and 273 cases by FISH. Eleven cases were positive or possibly positive by either IHC or FISH, and three cases were positive or possibly positive by both methods. Three cases were ALK-positive by FISH on whole section validation. There was no correlation between semi-quantitative IHC score (1+, 2+, 3+) and ALK rearrangement by FISH. The rabbit monoclonal anti-human CD246 clone D5F3 (Cell Signaling, Danvers, MA, USA) and the Novocastra mouse anti-ALK monoclonal 5A4 (Newcastle upon Tyne, UK) showed the greatest combination of 100% sensitivity with a specificity of 87.5% for 5A4 and 75% for D5F3 and neither produced false-negative results.

The authors concluded that IHC is a reliable screening tool for identification of ALK rearrangement in NSCLC and is antibody dependent. The D5F3 from Cell Signaling and 5A4 from Novocastra can be used with FISH for identification of IHC-positive cases to reduce screening costs. In addition, all cases exhibiting ALK rearrangement demonstrated adenocarcinoma histology and the results report a sensitivity of 100% and high specificity with the IHC with no false-negative results. The study was published in the January 2013 issue of the Journal of Thoracic Oncology.

Related Links:
University of British Columbia
Leica Microsystems
Cell Signaling