Iranian Journal of Pathology

Frequency of the L858R Mutation in Exon 21 of the Epidermal Growth Factor Receptor in Patients with Non-Small Cell Lung Cancer

Document Type : Original Research

Authors

Hossein Ayatollahi 1
Amir Hossein Jafarian 1, 2
Zohreh Emamdadi 2
Farideh Ranjbar 2
Hassan Mehrad-Majd 1, 3
Batul Oudi 2

1 Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Clinical Research Development Unit, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.

https://doi.org/10.30699/ijp.2025.2057190.3438
Abstract
Background & Objective: Epidermal growth factor receptor (EGFR) mutations are among the most common oncogenic drivers in non-small cell lung cancer (NSCLC). The L858R mutation in exon 21 of the EGFR gene is associated with responsiveness to targeted therapies in NSCLC patients. This study aimed to evaluate the frequency of L858R mutation and its correlation with clinicopathological characteristics in NSCLC patients.
Methods: In this cross-sectional study, Allele-specific Polymerase Chain Reaction (ASPCR) was used to detect L858R mutation in genomic DNA obtained from 336 patients diagnosed with NSCLC. Patients were categorized into mutation-positive groups and mutation-negative subgroups. Associations between the L858R mutation, clinicopathological features, and overall survival were analyzed using appropriate statistical methods.
Results: The L858R mutation was identified in 6% of patients (20 out of 336) and showed no significant association with clinicopathological features such as age, gender, tumor grade, histology subtypes, or metastasis (all P > 0.05). Survival analysis indicated an overall mortality rate of 81.8%, with no statistically significant difference in median survival between mutation-negative (11 months) and mutation-positive groups (8 months, P=0.246). Cox regression analysis identified Tumor Grade I as a b significant prognostic factor in both Univariate (HR=0.46, P=0.031) and multivariate (HR=0.46, P=0.040) models.
Conclusion: The frequency of the L858R mutation in this Iranian cohort with NSCLC was lower than that reported in global studies. However, its association with metastasis and mortality indicates the potential clinical relevance of this mutation in treatment planning.

Keywords

non-small cell lung cancer
epidermal growth factor receptor
L858R mutation
exon 21
clinicopathological features

Subjects

Copyright © 2026. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license also allows users to adapt, remix, transform, and build upon the material for any purpose, including commercial use.

 
 
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Iranian Journal of Pathology
Volume 21, Issue 1
Winter 2026
Pages 3-10

  • Receive Date 05 April 2025
  • Revise Date 06 August 2025
  • Accept Date 10 October 2025

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