Clinical and epidemiological study of EGFR mutations and EML4-ALK fusion genes among Indian patients with adenocarcinoma of the lung

Abstract

BackgroundMutation in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) is a common feature observed in lung adenocarcinoma. A fusion gene between echinoderm microtubule-associated protein-like 4 (EML4) and the intracellular domain of anaplastic lymphoma kinase (ALK), named EML4-ALK, has been identified in a subset of non-small-cell lung cancer (NSCLC) tumors. The objective of this study was to determine the prevalence of EGFR mutations and EML4-ALK fusions in Indian patients with NSCLC (adenocarcinoma) as well as evaluate their clinical characteristics.Patients and methodsPatients with NSCLC, adenocarcinoma histology, whose tumors had been tested for EGFR mutational status, were considered for this study. ALK gene rearrangement was detected by fluorescence in situ hybridization using the Vysis ALK Break Apart Rearrangement Probe Kit. ALK mutation was tested in samples that were negative for EGFR mutation.ResultsA total of 500 NSCLC adenocarcinoma patients were enrolled across six centers. There were 337 (67.4%) men and 163 (32.6%) women with a median age of 58 years. One hundred and sixty-four (32.8%) blocks were positive for EGFR mutations, whereas 336 (67.2%) were EGFR wild-type. Of the 336 EGFR-negative blocks, EML4-ALK fusion gene was present in 15 (4.5%) patients, whereas 321 (95.5%) tumors were EML4-ALK negative. The overall incidence of EML4-ALK fusion gene was 3% (15/500).ConclusionThe incidence of EGFR mutations (33%) in this Indian population is close to the reported incidence in Asian patients. EML4-ALK gene fusions are present in lung adenocarcinomas from Indian patients, and the 3% incidence of EML4-ALK gene fusion in EGFR mutation-negative cases is similar to what has been observed in other Western and Asian populations. The mutual exclusivity of EML4-ALK and EGFR mutations suggests implementation of biomarker testing for tumors harboring ALK rearrangements in order to identify patients that can benefit from newer targeted therapies.

Outcomes in Lung Cancer: 9-Year Experience From a Tertiary Cancer Center in India

“…Evaluation of tumors for EGFR mutation was started in 2012; at that time, 132 patients were examined and 46% of tumors were positive for an EGFR mutation. This is higher than in other studies performed in India by Doval et al (33%) 13 and Bhatt et al (31.3%), 9 possibly as a result of selection bias because the testing was aimed more at female patients and never-smokers. In the study titled “First Line IRESSA Versus Carboplatin/Paclitaxel in Asia (IPASS)” in East Asia in which only a selected population of nonsmokers with adenocarcinoma of the lung were included, EGFR mutations were present in 59.7%.…”

“…This is higher compared with results from other centers (2.7% to 3%) in India. 13 , 15 This might be a result of the use of immunohistochemstry rather than fluorescent in situ hybridization for detecting translocations. 16 …”

Clinicopathological and molecular epidemiological study of lung cancer patients seen at a tertiary care hospital in Northern India

“…The genetic heterogeneity has been reported not only across different countries but also among different ethnic regions within a country. [ 20 33 34 35 36 ] The incidence of EGFR mutation in NSCLC has been reported higher (47%) for Asian population as compared to their Caucasian (13%) counterparts. [ 37 ] A further higher incidence of EGFR mutation (23.2%–51.8%) in Indian NSCLC patients has been reported by various studies from India.…”

Lung cancer in the Indian subcontinent

“…[ 15 ] Another retrospective analysis involving 500 patients treated at six different centers revealed a slightly higher EGFR mutation rate of 33%. [ 16 ] Regional differences have also been reported, with a higher incidence of 65% in the Southern Indian population as compared to 33% in Northern Indian population. [ 17 ] These variations may be related to difference in smoking rates in the community.…”