Siqueira Juliana Mota, Heguedusch Daniele, Cunha Mateus Trinconi, de Sousa Luana Guimaraes, Marques-Piubelli Mario L, Carvalho Giovanna Lopes, Hoff Camilla Oliveira, Bonini Flavia, Mitani Yoshitsugu, Spiotto Michael T, Goepfert Ryan, Nunes Fabio Daumas, Matos Leandro Luongo, Kowalski Luiz Paulo, McGrail Daniel J, El-Naggar Adel K, Ferrarotto Renata
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA; Department of Stomatology, Discipline of Oral and Maxillofacial Pathology, School of Dentistry, University of São Paulo, São Paulo, SP, Brazil.
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Oral Oncol. 2025 Aug 26;169:107634. doi: 10.1016/j.oraloncology.2025.107634.
Oropharyngeal squamous cell carcinoma (OPSCC) presents prognostic and therapeutic challenges. Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein involved in oncogenic signaling pathways and has been explored as a therapeutic target in many solid tumors. This study aims to evaluate the prevalence and prognostic significance of TROP2 expression in OPSCC and explore its association with the tumor immune microenvironment composition. A cohort of 112 OPSCC patients from two high-volume cancer centers was retrospectively analyzed. TROP2 expression was assessed by immunohistochemistry and categorized into negative/low versus moderate/high. Transcriptomic analysis was performed in a subset of samples to explore immune microenvironment correlations. Survival analyses were conducted using Kaplan-Meier curves and Cox regression models. Moderate/high TROP2 expression was observed in 42 % of patients and was significantly associated with lower levels of smoking and alcohol exposure, reduced rates of perineural invasion, and fewer positive lymph nodes. Patients with moderate/high TROP2 expression demonstrated a trend toward improved overall survival (OS) (HR = 0.54, P = 0.07) and significantly prolonged disease-free survival (DFS) (HR = 0.46, P = 0.03). In TCGA validation Kaplan-Meier survival analysis demonstrated that patients with high TROP2 gene expression had significantly improved OS compared to those with low TROP2 expression (P = 0.012, HR = 0.361 [0.14-0.93]). Transcriptomic analysis revealed an enrichment of cytotoxic immune populations in tumors with high TROP2 expression. In OPSCC patients, high TROP2 expression was associated with more favorable pathologic characteristics, improved DFS, and a higher presence of cytotoxic immune cells in the tumor microenvironment.
口咽鳞状细胞癌（OPSCC）带来了预后和治疗方面的挑战。滋养层细胞表面抗原2（TROP2）是一种参与致癌信号通路的跨膜糖蛋白，已被探索作为多种实体瘤的治疗靶点。本研究旨在评估TROP2表达在OPSCC中的发生率和预后意义，并探讨其与肿瘤免疫微环境组成的关联。对来自两个大型癌症中心的112例OPSCC患者队列进行了回顾性分析。通过免疫组织化学评估TROP2表达，并分为阴性/低表达与中度/高表达。对一部分样本进行转录组分析以探索免疫微环境相关性。使用Kaplan-Meier曲线和Cox回归模型进行生存分析。42%的患者观察到中度/高TROP2表达，且与较低的吸烟和饮酒水平、较低的神经周围侵犯率以及较少的阳性淋巴结显著相关。中度/高TROP2表达的患者显示出总生存期（OS）改善的趋势（HR = 0.54，P = 0.07）和无病生存期（DFS）显著延长（HR = 0.46，P = 0.03）。在TCGA验证的Kaplan-Meier生存分析中，TROP2基因高表达的患者与TROP2低表达的患者相比，OS显著改善（P = 0.012，HR = 0.361[0.
