Molecular landscape of HER2-mutated non-small cell lung cancer in Northeastern Brazil: Clinical, histopathological, and genomic insights
Year: 2025
Type: article
Study design: Observational Study
Abstract: // Cleto Dantas Nogueira 1 , 2 , * , Samuel Frota 2 , * , Huylmer Lucena Chaves 6 , Juliana Cordeiro de Sousa 3 , Guilherme de Sousa Veloso 1 , 2 , Francisco Jonathan dos Santos Araujo 3 , Gabriel Barbosa Silva 1 , 2 , Samuel Silva Ferreira 2 , Marclesson Santos Alves 4 , Fabio Nasser 7 , Ezequiel Rangel 4 , Francisco Martins Neto 4 , Iusta Caminha 1 , Ellen Nascimento 5 and Fabio Tavora 1 , 2 , 4 1 Postgraduate Program in Pathology, Federal University of Ceará, Fortaleza, Brazil 2 Argos Pathology Laboratory, Fortaleza, Brazil 3 Postgraduate Program in Natural Resources Biotechnology, Center for Agricultural Sciences, Federal University of Ceará, Fortaleza, Brazil 4 Department of Pathology, Messejana Heart and Lung Hospital, Fortaleza, Brazil 5 InCor-HCFMUSP, São Paulo, Brazil 6 Thoracic Division, São Carlos Imagem Hospital, Fortaleza, Brazil 7 Institute D'Or for Research and Education, Fortaleza, Brazil * These authors contributed equally to this work Correspondence to: Fabio Tavora, email: [email protected] Keywords: HER2 mutation; NSCLC; lung cancer; targeted therapy; genomic profiling Received: December 17, 2024 Accepted: May 28, 2025 Published: June 17, 2025 Copyright: © 2025 Nogueira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT HER2 genomic alterations characterize a specific subset of NSCLC with potential therapeutic relevance. While most studies focus on populations from high-income countries, data from Latin America remains scarce. We retrospectively analyzed 13 HER2-mutated NSCLC cases from a single institution in Northeastern Brazil, integrating clinical, histopathological, immunohistochemical, and molecular findings. Predominant histological patterns included acinar and lepidic subtypes, with HER2 mutations primarily involving exon 20 insertions (A775_G776insYVMA) and frequent co-alterations in TP53, KRAS, and STK11. HER2 protein expression assessed by IHC showed low scores (0–2+) in most cases, while HER2 gene amplification was confirmed in one case by D-DISH and NGS. Tumor mutation burden was universally low. Treatment responses varied, with one patient receiving trastuzumab deruxtecan. Our findings highlight the molecular diversity and diagnostic challenges of HER2-mutated NSCLC in underrepresented populations, emphasizing the need for comprehensive molecular profiling and expanded access to targeted therapies.
Source: Oncotarget
Authors: Cleto Dantas Nogueira, Samuel Frota, Huylmer Lucena Chaves, Juliana Cordeiro de Sousa, Guilherme de Sousa Veloso, Francisco Jonathan dos Santos Araujo, Gabriel Barbosa Silva, Samuel Silva Ferreira, Marclesson Santos Alves, Fabio Nasser, Ezequiel Rangel, Francisco Martins Neto, Iusta Caminha, Ellen Nascimento, Fabio Tavora
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4411371500