Peter P. Luk, Christina I. Selinger, Annabelle Mahar, and Wendy A. Cooper (2018) Biomarkers for ALK and ROS1 in Lung Cancer: Immunohistochemistry and Fluorescent In Situ Hybridization. Archives of Pathology & Laboratory Medicine: August 2018, Vol. 142, No. 8, pp. 922-928.

SPECIAL SECTION—2017 (10TH BIENNIAL) MEETING OF THE PULMONARY PATHOLOGY SOCIETY, PART I

Biomarkers for ALK and ROS1 in Lung Cancer: Immunohistochemistry and Fluorescent In Situ Hybridization

Peter P. Luk, MBBS; Christina I. Selinger, PhD; Annabelle Mahar, MBBS; Wendy A. Cooper, MBBS, PhD

From the Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia (Drs Luk, Selinger, Mahar, and Cooper); Central Clinical School, University of Sydney, Sydney, Australia (Dr Cooper); and the School of Medicine, Western Sydney University, Sydney, Australia (Dr Cooper).

The authors have no relevant financial interest in the products or companies described in this article.

The manuscript is based on an invited talk presented at the Pulmonary Pathology Society Biennial Meeting; June 14, 2017; Chicago, Illinois.

Corresponding author: Wendy A. Cooper, MBBS, PhD, Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown NSW 2050, Australia (email: Wendy.Cooper@health.nsw.gov.au).

Context.— A small proportion of non–small cell lung cancers harbor rearrangements of ALK or ROS1 genes, and these tumors are sensitive to targeted tyrosine kinase inhibitors. It is crucial for pathologists to accurately identify tumors with these genetic alterations to enable patients to access optimal treatments and avoid unnecessary side effects of less effective agents. Although a number of different techniques can be used to identify ALK- and ROS1-rearranged lung cancers, immunohistochemistry and fluorescence in situ hybridization are the mainstays.

Objective.— To review the role of immunohistochemistry in assessment of ALK and ROS1 rearrangements in lung cancer, focusing on practical issues in comparison with other modalities such as fluorescence in situ hybridization.

Data Sources.— This manuscript reviews the current literature on ALK and ROS1 detection using immunohistochemistry and fluorescence in situ hybridization as well as current recommendations.

Conclusions.— Although fluorescence in situ hybridization remains the gold standard for detecting ALK and ROS1rearrangement in non–small cell lung cancer, immunohistochemistry plays an important role and can be an effective screening method for detection of these genetic alterations, or a diagnostic test in the setting of ALK.