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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
New insights into anaplastic lymphoma kinase-positive nonsmall cell lung cancer
A P Dubey1, N Pathi1, S Viswanath1
1Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India.
Background:
A novel fusion gene of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) has been identified in a subset of non-small-cell lung cancers (NSCLCs). Patients with the ALK-EML4 fusion gene demonstrate unique clinicopathological and physiological characteristics. Here we present an analysis of clinicopathological profile of patients of metastatic adenocarcinoma harboring the ALK-EML4 fusion gene and their response to targeted therapy in the form of crizotinib.
Methods:
A retrospective analysis of advanced ALK positive NSCLC, who presented at this tertiary care hospital of armed forces from September 2014 to December 2016 was conducted. The primary goal was to evaluate demographic and clinicopathological profile of ALK positive advanced NSCLC. Detection of ALK fusion was done by IHC on formalin fixed paraffin embedded cell blocks. Out of 20 ALK positive patients, ten patients received upfront cytotoxic chemotherapy, and rest received crizotinib. Patients progressing on cytotoxic chemotherapy received crizotinib as subsequent therapy.
Results:
Out of 270 patients of NSCLC, fifteen(7.4%) tested positive for ALK-EML4 fusion. Rate of positivity was higher in females(13.7%) than in males (5%). The correlation of the ALK-EML4 fusion gene and clinicopathological characteristics of NSCLC patients demonstrated a significant difference in smoking status, histological types, stage, & metastatic pattern. Median PFS with first line cytotoxic chemotherapy was 5.9 months. Median PFS with upfront crizotinib was not reached, but was significantly superior than cytotoxic chemotherapy.
Conclusion:
Our analysis indicated that ALK-EML4 positive NSCLC comprised a unique subgroup of adenocarcinomas with distinct clinicopathological characteristics. Incidence of ALK positivity was found to be higher in females and never smokers. These patients have distinct pathological and radiological characteristics. Crizotinib, whether used upfront or as subsequent therapy was found to be superior in PFS (not yet reached at the time of writing this article), and maintaining quality of life as compared to cytotoxic chemotherapy.
Insights
Patients with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion-positive non-small-cell lung cancer (NSCLC) have unique characteristics. Crizotinib demonstrated superior progression-free survival compared to chemotherapy in this NSCLC subgroup.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- A novel echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene is identified in a subset of non-small-cell lung cancers (NSCLCs).
- Patients with the ALK-EML4 fusion gene exhibit distinct clinicopathological and physiological features.
- This study analyzes the clinicopathological profile and targeted therapy response in metastatic adenocarcinoma patients with the ALK-EML4 fusion gene.
Purpose of the Study:
- To evaluate the demographic and clinicopathological profile of advanced ALK-positive NSCLC patients.
- To assess the response to crizotinib targeted therapy in ALK-EML4 positive NSCLC.
- To compare the efficacy of crizotinib with cytotoxic chemotherapy in advanced NSCLC.
Main Methods:
- Retrospective analysis of advanced ALK-positive NSCLC patients from September 2014 to December 2016.
- ALK fusion detection using immunohistochemistry (IHC) on formalin-fixed paraffin-embedded cell blocks.
- Comparison of outcomes between patients receiving upfront cytotoxic chemotherapy and those receiving crizotinib (upfront or subsequent therapy).
Main Results:
- Fifteen out of 270 (7.4%) NSCLC patients tested positive for ALK-EML4 fusion, with higher prevalence in females (13.7%) than males (5%).
- ALK-EML4 fusion correlated significantly with smoking status, histology, stage, and metastatic pattern.
- Median progression-free survival (PFS) with crizotinib was not reached and was significantly superior to the 5.9 months PFS with first-line cytotoxic chemotherapy.
Conclusions:
- ALK-EML4 positive NSCLC represents a distinct subgroup of adenocarcinomas with unique characteristics.
- Higher incidence of ALK positivity was observed in females and never-smokers.
- Crizotinib showed superior PFS and maintained quality of life compared to cytotoxic chemotherapy in ALK-EML4 positive NSCLC.
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