---
title: "Stepwise Molecular Profiling Reveals Co-occurring EGFR L858R and HER2 Amplification in NSCLC"
id: "pubmed-42681853"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42681853"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42681853/"
doi: "10.12659/AJCR.953829"
published_at: "2026-09-02T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Stepwise Molecular Profiling Reveals Co-occurring EGFR L858R and HER2 Amplification in NSCLC
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42681853
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42681853/)
- **DOI:** [10.12659/AJCR.953829](https://doi.org/10.12659%2FAJCR.953829)
- **Published At:** 2026-09-02T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- A 54-year-old non-smoking woman was diagnosed with Stage IIIA lung adenocarcinoma in 2020. Initial PCR-based testing was negative for **EGFR** mutations. - After disease progression with brain metastases and severe chemotherapy toxicity, further testing in a resource-limited setting identified **HER2 (ERBB2) amplification** by **FISH**. - The patient received **trastuzumab** and achieved 23 months of clinical and radiologic stabilization attributed to HER2-targeted therapy. - Archived tumor tissue was later analyzed by **NGS**, which detected a previously unrecognized **EGFR L858R** mutation. - New pulmonary lesions emerged in late April 2025, consistent with disease progression; based on the verified EGFR L858R result, **gefitinib** was initiated in May 2025. - The case highlights that limited initial PCR testing can miss co-occurring actionable drivers, that stepwise molecular profiling (FISH then NGS) can identify additional targets even in resource-constrained settings, and that sequential therapeutic responses support clinical relevance of both HER2 amplification and EGFR L858R in this patient. - The authors note that conclusions about diagnostic sequencing or oncogenic driver hierarchy cannot be generalized from a single case; some methodological and contextual details were not reported in the abstract.
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Affiliations Expand ### Affiliations * 1 Department of Chemotherapy, Kazakh Research Institute of Oncology and Radiology (KazRIOR), Almaty, Kazakhstan. * 2 Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan. * 3 Almaty Oncology Center, Almaty, Kazakhstan. * 4 National Scientific Oncology Center, Astana, Kazakhstan. * PMID: **42681853** * DOI: [ 10.12659/AJCR.953829 ](https://doi.org/10.12659/ajcr.953829) Item in Clipboard Case Reports # Co-Occurring EGFR L858R Mutation and HER2 Amplification in NSCLC Identified by Stepwise Molecular Profiling Rabiga Kadyrbayeva et al. Am J Case Rep. 2026. Show details Display options Display options Format Abstract PubMed PMID Am J Case Rep Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Am+J+Case+Rep%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Am+J+Case+Rep%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42681853/) . 2026 Sep 2:27:e953829. doi: 10.12659/AJCR.953829. ### Authors [Rabiga Kadyrbayeva](https://pubmed.ncbi.nlm.nih.gov/?term=Kadyrbayeva+R&cauthor_id=42681853)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42681853/#short-view-affiliation-1 "Department of Chemotherapy, Kazakh Research Institute of Oncology and Radiology \(KazRIOR\), Almaty, Kazakhstan.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42681853/#short-view-affiliation-2 "Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan."), [Dilyara Kaidarova](https://pubmed.ncbi.nlm.nih.gov/?term=Kaidarova+D&cauthor_id=42681853)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42681853/#short-view-affiliation-2 "Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan."), [Aisha Moldasheva](https://pubmed.ncbi.nlm.nih.gov/?term=Moldasheva+A&cauthor_id=42681853)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42681853/#short-view-affiliation-1 "Department of Chemotherapy, Kazakh Research Institute of Oncology and Radiology \(KazRIOR\), Almaty, Kazakhstan."), [Kaldygul Kabakovna Smagulova](https://pubmed.ncbi.nlm.nih.gov/?term=Smagulova+KK&cauthor_id=42681853)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42681853/#short-view-affiliation-1 "Department of Chemotherapy, Kazakh Research Institute of Oncology and Radiology \(KazRIOR\), Almaty, Kazakhstan."), [Innara Turkpenova](https://pubmed.ncbi.nlm.nih.gov/?term=Turkpenova+I&cauthor_id=42681853)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42681853/#short-view-affiliation-1 "Department of Chemotherapy, Kazakh Research Institute of Oncology and Radiology \(KazRIOR\), Almaty, Kazakhstan."), [Madina Orazgalieva](https://pubmed.ncbi.nlm.nih.gov/?term=Orazgalieva+M&cauthor_id=42681853)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42681853/#short-view-affiliation-1 "Department of Chemotherapy, Kazakh Research Institute of Oncology and Radiology \(KazRIOR\), Almaty, Kazakhstan."), [Saniya Omirkhanovna Ossikbayeva](https://pubmed.ncbi.nlm.nih.gov/?term=Ossikbayeva+SO&cauthor_id=42681853)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42681853/#short-view-affiliation-1 "Department of Chemotherapy, Kazakh Research Institute of Oncology and Radiology \(KazRIOR\), Almaty, Kazakhstan."), [Elvira Satbayeva](https://pubmed.ncbi.nlm.nih.gov/?term=Satbayeva+E&cauthor_id=42681853)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42681853/#short-view-affiliation-3 "Almaty Oncology Center, Almaty, Kazakhstan."), [Valeriy Makarov](https://pubmed.ncbi.nlm.nih.gov/?term=Makarov+V&cauthor_id=42681853)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42681853/#short-view-affiliation-4 "National Scientific Oncology Center, Astana, Kazakhstan.") ### Affiliations * 1 Department of Chemotherapy, Kazakh Research Institute of Oncology and Radiology (KazRIOR), Almaty, Kazakhstan. * 2 Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan. * 3 Almaty Oncology Center, Almaty, Kazakhstan. * 4 National Scientific Oncology Center, Astana, Kazakhstan. * PMID: **42681853** * DOI: [ 10.12659/AJCR.953829 ](https://doi.org/10.12659/ajcr.953829) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract BACKGROUND The coexistence of multiple oncogenic drivers in non-small cell lung cancer (NSCLC) is a rare and diagnostically challenging molecular configuration. Conventional polymerase chain reaction (PCR)-based testing may fail to detect co-occurring genomic alterations, potentially limiting therapeutic options, particularly in resource-constrained settings. CASE REPORT We describe the case of a 54-year-old non-smoking woman diagnosed with Stage IIIA lung adenocarcinoma in 2020. Initial PCR-based molecular testing was negative for EGFR mutations. Following disease progression with brain metastases and severe chemotherapy toxicity, stepwise molecular profiling in a resource-limited setting identified HER2 (ERBB2) amplification via fluorescence in situ hybridization (FISH). The patient achieved 23 months of clinical and radiological stabilization on trastuzumab. Subsequent next-generation sequencing (NGS) analysis of archived tissue revealed a previously undetected estimated glomular filtration rate (EGFR) L858R mutation. In late April 2025, new lesions appeared in the lungs, indicating disease progression. Based on the previously verified EGFR L858R mutation, the treatment strategy was revised and gefitinib was initiated in May 2025. CONCLUSIONS This case illustrates that co-occurring EGFR and HER2 alterations can remain undetected following initial limited molecular testing, and that stepwise molecular profiling in a resource-constrained setting can facilitate identification of therapeutically actionable targets. The sequential clinical responses observed are consistent with the biological relevance of both alterations, although broader conclusions regarding diagnostic strategy or driver hierarchy cannot be drawn from a single observation. 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