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Reflex ALK immunohistochemistry is feasible and highly specific for ALK gene rearrangements in lung cancer

Houang, Michelle1,2,3; Toon, Christopher W.1,3,4; Clarkson, Adele1,2; Sioson, Loretta1,2; Watson, Nicole1; Farzin, Mahtab1,2; Selinger, Christina I.5; Chou, Angela1,6; Morey, Adrienne L.6; Cooper, Wendy A.3,5,7; O’Toole, Sandra A.3,5,8; Gill, Anthony J.1,2,3

Pathology:
doi: 10.1097/PAT.0000000000000114
Anatomical Pathology
Abstract

Summary: Fluorescence in situ hybridisation (FISH) is considered the gold standard for the detection of ALK gene rearrangements in lung adenocarcinoma. The presence of ALK gene rearrangement predicts response to specific targeted therapy, but these rearrangements are relatively rare and FISH studies are expensive, not widely available, potentially challenging to interpret and therefore difficult to undertake in all patients with non-small cell lung cancer. We developed and then deployed into the routine clinical setting a screening program for ALK gene rearrangement in all non-small cell lung cancer patients based on immunohistochemistry (IHC) with a mouse monoclonal antibody (clone 5A4).

ALK IHC was strongly positive in 12 (4%) of 307 tumours from consecutive patients. Only 10 of these cancers were initially thought to be rearranged by diagnostic FISH studies. The two tumours which were IHC positive but initially interpreted as FISH negative underwent repeat FISH testing because of the discrepancy. Repeat FISH testing confirmed the presence of ALK gene rearrangement with the discrepancy being attributable to an atypical FISH pattern.

Therefore, in our experienced hands, IHC for ALK performed on initial diagnosis of lung cancer is 100% specific for the presence of ALK gene rearrangement. When ALK IHC and FISH studies are discrepant, IHC may outperform FISH. Although our study was not intended to formally assess the sensitivity of ALK IHC, the 4% rate of gene rearrangements identified by this approach is consistent with the expected incidence in our population.

We conclude that reflex ALK IHC followed by confirmatory FISH testing can be readily integrated into the routine clinical setting and represents a cost effective and practical approach to screening for these clinically significant gene rearrangements.

Author Information

1Cancer Diagnosis and Pathology Group, Northern Translational Cancer Research Unit, Kolling Institute of Medical Research, St Leonards

2Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards

3Sydney Medical School, University of Sydney, Sydney

4HistoPath Pathology, North Ryde

5Department of Tissue Oncology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown

6Department of Anatomical Pathology, SydPath, St Vincent's Hospital, Darlinghurst

7School of Medicine, University of Western Sydney

8Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia

Address for correspondence: Dr A. J. Gill, Department of Anatomical Pathology, Royal North Shore Hospital, Pacific Highway, St Leonards, NSW 2065, Australia. E-mail: affgill@med.usyd.edu.au

Received 5 December, 2013

Revised 13 January, 2014

Accepted 14 January, 2014

© 2014 Royal College of Pathologists of Australasia

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