口咽鳞状细胞癌中TROP2和Nectin-4的表达模式与HPV状态的关系：靶向治疗的潜在生物标志物
Expression patterns of TROP2 and Nectin-4 in oropharyngeal squamous cell carcinoma in relation to HPV status: potential biomarkers for targeted therapy.
作者信息
Klasen Charlotte, Eckel Hans N C, Wuerdemann Nora, Böckelmann Joseph, Knipper Karl, Suchan Malte, Sharaf Kariem, Sharma Shachi Jenny, Abing Helen, Charpentier Arthur, Esser Julia, Hansen Kevin, Mayer Marcel, Jansen Louis, Klußmann Jens Peter, Quaas Alexander, Lyu Su Ir
机构信息
Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine and University Hospital Cologne, Kerpernerstraße 62, Cologne 50923, Germany Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
出版信息
Ther Adv Med Oncol. 2025 Aug 18;17:17588359251361877. doi: 10.1177/17588359251361877. eCollection 2025.
BACKGROUND
Patients with inoperable or metastatic oropharyngeal squamous cell carcinoma (OSCC) face limited therapeutic options. Nectin-4, an immunoglobulin-like transmembrane adhesion protein, and Trophoblast Surface Antigen 2 (TROP2), a transmembrane glycoprotein, have recently emerged as targets for antibody-drug conjugates (ADCs). , an ADC targeting Nectin-4, has been approved for locally advanced or metastatic urothelial carcinoma, while , targeting TROP2, was approved for metastatic triple-negative breast cancer.
OBJECTIVES
This study aimed to demonstrate expression rates of TROP2 and Nectin-4 in a representative cohort of human papillomavirus (HPV)-positive and HPV-negative OSCC and discuss the relevance of those markers as possible targets for ADCs.
DESIGN
A retrospective cohort study.
METHODS
We analyzed tissue samples from 226 OSCC patients treated at the University Hospital of Cologne between 2005 and 2020. The expression of Nectin-4 and TROP2 was assessed using immunohistochemistry, and the H-score method was applied to categorize expression levels into four groups: negative (0-10), low (11-100), moderate (101-200), and high (201-300).
RESULTS
TROP2 expression was positive in 96.5% of the samples, with 84.1% showing moderate to high expression (H-Score 101-300). A total of 38.8% of the cases expressed Nectin-4. Notably, patients with HPV-positive OSCC demonstrated significantly higher Nectin-4 expression compared to those with HPV-negative OSCC ( < 0.001).
CONCLUSION
This study is one of the first to investigate the expression of Nectin-4 and TROP2 in a cohort of both HPV-positive and HPV-negative OSCC patients. Our results indicate that TROP2 is almost universally expressed in OSCC, while Nectin-4 expression is less frequent. TROP2 and Nectin-4 are promising therapeutic targets for OSCC, with Nectin-4 being particularly relevant for HPV-positive patients. Clinical trials are necessary to confirm the clinical relevance and efficacy of ADCs targeting TROP2 and Nectin-4 in OSCC treatment.
背景
无法手术切除的、转移性口咽鳞状细胞癌（OSCC）患者的治疗选择有限。Nectin-4是一种免疫球蛋白样跨膜粘附蛋白，滋养层表面抗原2（TROP2）是一种跨膜糖蛋白，最近已成为抗体药物偶联物（ADC）的靶点。靶向Nectin-4的ADC已被批准用于局部晚期或转移性尿路上皮癌，而靶向TROP2的ADC已被批准用于转移性三阴性乳腺癌。
目的
本研究旨在证明TROP2和Nectin-4在一组具有代表性的人乳头瘤病毒（HPV）阳性和HPV阴性OSCC中的表达率，并讨论这些标志物作为ADC可能靶点的相关性。
设计
一项回顾性队列研究。
方法
我们分析了2005年至2020年期间在科隆大学医院接受治疗的226例OSCC患者的组织样本。使用免疫组织化学评估Nectin-4和TROP2的表达，并应用H评分法将表达水平分为四组：阴性（0-10）、低（11-100）、中度（101-200）和高（201-300）。
结果
96.5%的样本中TROP2表达呈阳性，84.1%表现为中度至高表达（H评分101-300）。共有38.8%的病例表达Nectin-4。值得注意的是，与HPV阴性的OSCC患者相比，HPV阳性的OSCC患者Nectin-4表达显著更高（<0.001）。
结论
本研究是最早调查Nectin-4和TROP2在一组HPV阳性和HPV阴性OSCC患者中表达情况的研究之一。我们的结果表明，TROP2在OSCC中几乎普遍表达，而Nectin-4表达频率较低。TROP2和Nectin-4是OSCC有前景的治疗靶点，Nectin-4对HPV阳性患者尤为重要。需要进行临床试验以确认靶向TROP2和Nectin-4的ADC在OSCC治疗中的临床相关性和疗效。
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