LBA1 - Establishment of a diagnostic algorithm for ROS1 testing in Canada

Date 07 May 2017
Event ELCC 2017
Session ESMO-IASLC Best Abstracts
Topics Thoracic malignancies
Presenter Ming Tsao
Citation Annals of Oncology (2017) 28 (suppl_2): ii69-ii70. 10.1093/annonc/mdx195
Authors M.S. Tsao1, E. Torlakovic2, G. Bigras3, H. Wang4, G. Qing5, C.C. Cheung6, Z. Xu7, C. Couture8, D. Ionescu9, A. Smith6
  • 1Pathology, Princess Margaret Cancer Centre, M5G1L7 - Toronto/CA
  • 2Anatomic Pathology, William Osler Health System, M9V 1R8 - Etobicoke/CA
  • 3Pathology, University of Alberta Cross Cancer Institute, Edmonton/CA
  • 4Pathology, Jewish General Hospital McGill University, Montreal/CA
  • 5Pathology, Winnipeg Health Sciences Centre-CancerCare Manitoba, Winnipeg/CA
  • 6Pathology, University Health Network, Toronto/CA
  • 7Pathology, Capital District Health Authority Queen Elizabeth II Health Sciences Centre, Halifax/CA
  • 8Pathology, Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Quebec City/CA
  • 9Pathology, British Columbia Cancer Agency, Vancouver/CA

Abstract

Background

The ROS1 fusion tyrosine kinase that results from rearrangements of the ROS1 gene is a new targetable driver oncogene. It is detected in 1-2% of lung adenocarcinoma patients. Crizotinib recently received US FDA approval for the treatment of patients with lung cancer carrying ROS1 rearrangements. Fluorescent in situ hybridization (FISH) is the gold standard for detecting ROS1 rearranged tumors. Immunohistochemistry (IHC) has been considered as a screening assay to identify ROS1 rearranged lung cancers. However, published reports suggested that ROS1 IHC shows high sensitivity but moderate specificity, thus resulting in a high percentage of cases that require confirmatory FISH testing. This may negatively impact on the cost of ROS1 screening by IHC.

Methods

Sensitive and highly specific IHC protocols for ROS1 testing using D4D6 antibody (Cell Signaling, Danver, MA) on the Ventana and Dako autostainers were developed. A FISH protocol for detecting ROS1 gene rearrangements using a ROS1 (6q22) Break Apart FISH Probe (Biocare, Concord, CA) was also established. A network of 14 pathology laboratories participated in the validation of these protocols to detect ROS1 rearranged lung cancers. Validation involved 9 confirmed ROS1 FISH positive (+) and 15 ROS1 FISH negative (-) tumor samples.

Results

Among 10 laboratories that completed FISH testing, 11 (4.6%) of 240 tests failed. The overall sensitivity of the laboratories to detect FISH+ cases was 88.9% (80/90), and the misclassification rate was 3.5% (8/229). Among 11 laboratories that completed the IHC testing, results from 14/264 (5.3%) tests were unavailable. Using the H-score cut-off of 80 (that completely distinguished between the mean H-score of FISH+ and FISH- cases), the overall sensitivity to detect FISH+ sample was 97%, with 94% specificity, 91% positive predictive value, and 98% negative predictive value. Eight laboratories achieved 100% sensitivity; only one laboratory had specificity below 90%. ROS1 IHC positive tumor showed homogeneous staining in practically all tumor cells.

Conclusions

This pan-Canadian consortium established the criteria to enable clinical implementation of IHC screening and FISH testing for ROS1 rearranged lung cancers using optimized protocols with high sensitivity and specificity.

Clinical trial identification

Legal entity responsible for the study

University Health Network

Funding

Pfizer Canada

Disclosure

M.S. Tsao: Received advisory board honoraria and research grant from Pfizer Canada, AstraZeneca, Merck Canada. Received advisory board honoraria from Bristol-Myers Squibb, Hoffmann La Roche and Boehringer Ingelheim Canada. E. Torlakovic: Received advisory board honoraria from Pfizer Canada, Merck Canada, Bristol-Myers Squibb. G. Bigras: Received advisory board honoraria from Pfizer Canada, Merck Canada, Bristol-Myers Squibb. H. Wang: Received advisory board honoraria from Pfizer Canada, Merck Canada, Bristol-Myers Squibb and Hoffmann La Roche Canada. G. Qing: Received advisory board honoraria from Pfizer Canada, Merck Canada, Bristol-Myers Squibb. C.C. Cheung: Received advisory board honoraria from Merck Canada and Bristol-Myers Squibb. Z. Xu: Received advisory board honoraria from Pfizer Canada, Merck Canada, Bristol-Myers Squibb, Hoffmann La Roche. C. Couture, D. Ionescu: Received advisory board honoraria from Pfizer Canada, AstraZeneca, Merck Canada, Bristol-Myers Squibb, Hoffmann La Roche. A. Smith: Received advisory board honoraria from Pfizer Canada