Interpretive Handbook

Test 62457 :
Lung Cancer, ROS1 (6q22) Rearrangement, FISH, Tissue

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Lung cancer is the leading cause of cancer mortality in developed countries. The discovery of a variety of genetic alterations in non-small-cell lung cancer (NSCLC) has enabled the use of targeted therapy such as the anaplastic lymphoma kinase (ALK) inhibitor, crizotinib, and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, erlotinib, for NSCLC with ALK rearrangements and EGFR mutations, respectively.


The c-ros oncogene 1 (ROS1), originally described in glioblastomas, has been identified as a potential relevant therapeutic target in lung adenocarcinoma. Crizotinib has shown in vitro activity and early evidence of clinical activity in ROS1-rearranged tumors.

Useful For Suggests clinical disorders or settings where the test may be helpful

Identifying ROS1 gene rearrangements in patients with late-stage, lung adenocarcinomas that are negative for EGFR mutations and ALK rearrangements

Interpretation Provides information to assist in interpretation of the test results

A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal cutoff for the probe set.


A positive result suggests rearrangement of the ROS1 locus and a tumor that may be responsive to ALK-inhibitor therapy. A negative result suggests no rearrangement of the ROS1 gene region at 6q22.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test is not approved by the FDA, and it is best used as an adjunct to existing clinical and pathologic information.


Fixatives other than formalin (eg, Prefer, Bouin) may not be successful for FISH assays. Although FISH testing will not be rejected due to nonformalin fixation, results may be compromised.


Paraffin-embedded tissues that have been decalcified are generally unsuccessful for FISH analysis. The pathologist reviewing the hematoxylin and eosin-stained slide may find it necessary to cancel testing.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Suehara Y, Arcila M, Wang L, et al: Identification of KIF5B-RET and GOPC-ROS1 fusions in lung adenocarcinomas through a comprehensive mRNA-based screen for tyrosine kinase fusions. Clin Cancer Res 2012;18(24):6599-6608

2. Takeuchi K, Soda M, Togashi Y, et al: RET, ROS1 and ALK fusions in lung cancer. Nat Med 2012;18(3):378-381

3. Bergethon K, Shaw AT, Ou SH, et al: ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol 2012;30(8):863-870

4. Chin LP, Soo RA, Soong R, Ou SH: Targeting ROS1 with anaplastic lymphoma kinase inhibitors: a promising therapeutic strategy for a newly defined molecular subset of non-small-cell lung cancer. J Thorac Oncol 2012;7(11):1625-1630