Nogueira Cleto Dantas, Frota Samuel, Chaves Huylmer Lucena, de Sousa Juliana Cordeiro, Veloso Guilherme de Sousa, Araujo Francisco Jonathan Dos Santos, Silva Gabriel Barbosa, Ferreira Samuel Silva, Alves Marclesson Santos, Nasser Fabio, Rangel Ezequiel, Neto Francisco Martins, Caminha Iusta, Nascimento Ellen, Tavora Fabio
Postgraduate Program in Pathology, Federal University of Ceará, Fortaleza, Brazil.
Argos Pathology Laboratory, Fortaleza, Brazil.
Oncotarget. 2025 Jun 17;16:467-479. doi: 10.18632/oncotarget.28737.
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.
HER2基因改变是具有潜在治疗相关性的非小细胞肺癌（NSCLC）的一个特定亚组的特征。虽然大多数研究集中于高收入国家的人群，但来自拉丁美洲的数据仍然稀缺。我们回顾性分析了巴西东北部一家单一机构的13例HER2突变的NSCLC病例，整合了临床、组织病理学、免疫组织化学和分子学发现。主要的组织学模式包括腺泡状和鳞屑状亚型，HER2突变主要涉及外显子20插入（A775_G776insYVMA），并且在TP53、KRAS和STK11中频繁出现共改变。通过免疫组织化学评估的HER2蛋白表达在大多数病例中显示低分（0-2+），而通过D-DISH和二代测序（NGS）在1例病例中证实了HER2基因扩增。肿瘤突变负荷普遍较低。治疗反应各不相同，1例患者接受了曲妥珠单抗德鲁替康治疗。我们的研究结果突出了HER2突变的NSCLC在代表性不足人群中的分子多样性和诊断挑战，强调了全面分子谱分析的必要性以及扩大靶向治疗可及性的需求。
