Molecular analysis for EGFR, ALK, and ROS1 alterations in over 3000 Indian patients with non-small-cell lung cancer: A retrospective observational study

Abstract

Background: Accurate molecular testing in non-small-cell lung cancer (NSCLC) is of paramount importance for treatment, prediction, and prognostication. Objectives: We aimed to comprehensively describe the clinicopathological and molecular profile of Indian patients with NSCLC with regard to alterations in the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and c-ros oncogene 1 (ROS1). Materials and Methods: We conducted a retrospective analysis of lung tissue samples tested between January 2015 and December 2021 at the Metropolis Healthcare Limited global referral laboratory facility in Mumbai, Maharashtra, India. Testing was conducted for EGFR by real time reverse transcriptase polymerase chain reaction (RT-PCR) and Sanger sequencing, ALK by immunohistochemistry (IHC), ALK by fluorescence in situ hybridization (FISH), and c-ros oncogene 1 (ROS1) by FISH. We analyzed the positivity status and determined the trends in the results of the molecular targets in NSCLC cases. Results: Out of 3220 samples with malignancy, 1750 (54.3%) were tested for EGFR, out of which 510 (29.1%) were positive. The most common mutation detected was in exon 19 of EGFR (334/510, 65.5%), followed by exon 21 (164/510, 32.2%). A total of 1548 (48.1%) cases were tested for ALK by IHC, of which 125/1548 (8.1%) showed positivity, while among the 372/3220 (11.6%) cases tested for ALK by FISH, 29/372 (7.8%) were positive. In patients with squamous cell carcinoma, the ALK positivity rate by IHC was 5.3%. Of the 372 cases tested for ALK by FISH, 353 (94.9%) cases were tested for ALK by IHC as well; 98.9% concordance was observed for the positive cases. ROS1 testing was conducted in 370/3220 (11.5%) samples and showed a low positivity rate of 13/370 (3.5%). Conclusions: Indian patients with NSCLC have 29% EGFR positivity, 8.1% ALK positivity, and 3.5% ROS1 positivity, when tested with RT-PCR, IHC, and FISH, respectively. A detailed molecular analysis using next-generation sequencing (NGS) may help detect a higher number of molecular targets amenable to therapy.