Testing for ROS1 in non-small cell lung cancer: a review with recommendations

• Published in: Virchows Archiv : an international journal of pathology Vol. 469; no. 5; pp. 489 - 503
• Main Authors: Bubendorf, Lukas, Büttner, Reinhard, Al-Dayel, Fouad, Dietel, Manfred, Elmberger, Göran, Kerr, Keith, López-Ríos, Fernando, Marchetti, Antonio, Öz, Büge, Pauwels, Patrick, Penault-Llorca, Frédérique, Rossi, Giulio, Ryška, Aleš, Thunnissen, Erik
• Format: Journal Article Book Review
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-11-2016; Springer Nature B.V
• Subjects: Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - genetics; Gene Rearrangement - genetics; Genetic screening; Humans; In situ tests; Lung cancer; Lung Neoplasms - diagnosis; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Medicine; Medicine & Public Health; Oncogenes - genetics; Pathology; Protein-Tyrosine Kinases - genetics; Proto-Oncogene Proteins - genetics; Receptor Protein-Tyrosine Kinases - genetics; Review and Perspectives; Review and s; Immunohistochemistry; Fluorescence in situ hybridisation; ROS1; RT-PCR; Non-small cell lung cancer; Predictive marker
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-016-2000-3

Rearrangements of the
ROS1
gene occur in 1–2 % of non-small cell lung cancers (NSCLCs). Crizotinib, a highly effective inhibitor of ROS1 kinase activity, is now FDA-approved for the treatment of patients with advanced
ROS1
-positive NSCLC. Consequently, focus on
ROS1
testing is growing. Most laboratories currently rely on fluorescence in situ hybridisation (FISH) assays using a dual-colour break-apart probe to detect
ROS1
rearrangements. Given the rarity of these rearrangements in NSCLC, detection of elevated ROS1 protein levels by immunohistochemistry may provide cost-effective screening prior to confirmatory FISH testing. Non-in situ testing approaches also hold potential as stand-alone methods or complementary tests, including multiplex real-time PCR assays and next-generation sequencing (NGS) platforms which include commercial test kits covering a range of fusion genes. In order to ensure high-quality biomarker testing, appropriate tissue handling, adequate control materials and participation in external quality assessment programmes are essential, irrespective of the testing technique employed.
ROS1
testing is often only considered after negative tests for
EGFR
mutation and
ALK
gene rearrangement, based on the assumption that these oncogenic driver events tend to be exclusive. However, as the use of ROS1 inhibitors becomes routine, accurate and timely detection of
ROS1
gene rearrangements will be critical for the optimal treatment of patients with NSCLC. As NGS techniques are introduced into routine diagnostic practice,
ROS1
fusion gene testing will be provided as part of the initial testing package.