ROS1 expression and translocations in non-small-cell lung cancer: clinicopathological analysis of 1478 cases

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Non-small-cell lung cancer (NSCLC) molecular profiling reveals actionable mutations for targeted therapy.
• Chromosomal rearrangements involving ROS1 (c-ros oncogene 1, receptor tyrosine kinase) are identified as a target for crizotinib treatment.

Purpose of the Study:

• To determine the clinicopathological characteristics of NSCLC associated with ROS1 expression and translocation.
• To evaluate the utility of ROS1 immunohistochemistry as a screening tool for identifying NSCLC patients eligible for targeted therapy.

Main Methods:

• Screening of 1478 NSCLC cases using a ROS1-specific antibody.
• Fluorescence in situ hybridization (FISH) to confirm ROS1 translocations in immunoreactive cases.
• Analysis of clinicopathological features, survival data, and molecular tumor composition in ROS1-positive NSCLC.

Main Results:

• ROS1 immunoreactivity was observed in 4.6% (68/1478) of NSCLC cases; ROS1 translocations were confirmed in 0.6% (9/1478).
• ROS1 expression was more frequent in female patients with adenocarcinoma, early tumor stages (low T stages), and associated with TTF1/napsin expression and specific histomorphological patterns.
• ROS1 translocations were found alongside other driver mutations (EGFR, KRAS, BRAF). ROS1 expression predicted favorable survival independently of tumor stage.

Conclusions:

• ROS1 translocations are infrequent in Caucasian NSCLC patients.
• Immunohistochemical screening for ROS1 expression, combined with clinicopathological parameters (female sex, early stage, adenocarcinoma with TTF1/napsin, specific histology), effectively enriches for cases with ROS1 alterations.
• Multistep molecular selection strategies may not be the most efficient approach for identifying patients for ROS1-targeted therapies.