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Expression patterns of TROP2 and Nectin-4 in oropharyngeal squamous cell carcinoma in relation to HPV status:
Charlotte Klasen1, Hans N C Eckel2,3, Nora Wuerdemann3,4
1Department 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.
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). Enfortumab Vedotin, an ADC targeting Nectin-4, has been approved for locally advanced or metastatic urothelial carcinoma, while sacituzumab govitecan, 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 (p < 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.
Insights
Trophoblast Surface Antigen 2 (TROP2) is highly expressed in oropharyngeal squamous cell carcinoma (OSCC), making it a promising target for antibody-drug conjugates (ADCs). Nectin-4 is also a potential target, especially in human papillomavirus (HPV)-positive OSCC.
Area of Science:
- Oncology
- Translational Research
- Molecular Diagnostics
Background:
- Limited therapeutic options exist for patients with inoperable or metastatic oropharyngeal squamous cell carcinoma (OSCC).
- Nectin-4 and Trophoblast Surface Antigen 2 (TROP2) are emerging targets for antibody-drug conjugates (ADCs) in cancer therapy.
- Existing ADCs targeting Nectin-4 and TROP2 have shown efficacy in other cancer types, such as urothelial carcinoma and triple-negative breast cancer.
Purpose of the Study:
- To determine the expression rates of TROP2 and Nectin-4 in a cohort of OSCC patients.
- To evaluate the differential expression of these markers in human papillomavirus (HPV)-positive versus HPV-negative OSCC.
- To assess the potential of TROP2 and Nectin-4 as therapeutic targets for ADCs in OSCC treatment.
Main Methods:
- Retrospective cohort study of 226 OSCC patients treated between 2005 and 2020.
- Immunohistochemistry was used to assess Nectin-4 and TROP2 expression.
- The H-score method categorized expression levels into negative, low, moderate, and high groups.
Main Results:
- TROP2 was expressed in 96.5% of OSCC samples, with 84.1% showing moderate to high expression.
- Nectin-4 was expressed in 38.8% of the samples.
- HPV-positive OSCC showed significantly higher Nectin-4 expression compared to HPV-negative OSCC (p < 0.001).
Conclusions:
- TROP2 is ubiquitously expressed in OSCC, representing a viable target for ADCs.
- Nectin-4 is also a potential target, particularly in HPV-positive OSCC.
- Further clinical trials are warranted to confirm the efficacy of TROP2- and Nectin-4-targeting ADCs in OSCC treatment.
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