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Trop2 Expression in Correlation to the Molecular Subtype in Vulvar Squamous Cell Carcinomas
Introduction:
Targeted therapy with antibody-drug conjugates (ADCs) has achieved promising results in the treatment of different solid tumors. Sacituzumab-Govitecan (SG), a humanized anti-Trop2 monoclonal antibody linked with the cytotoxic topoisomerase I inhibitor SN-38, has been approved for the treatment of metastatic triple-negative breast cancer. The treatment approach with SG requires the expression of Trop2 within the tumor cells. Trop2 is overexpressed in many other cancer types, suggesting a broader therapeutic application beyond breast cancer to these ADCs. We explore expression of Trop2 vulvar squamous cell carcinomas (VSCCs) and how this relates to molecular classification.
Methods:
Immunohistochemical Trop2 expression was evaluated on diagnostic biopsies of VSCC using an immunoreactive score. Staining results were compared to the molecular subtype of VSCC.
Results:
Fifty-seven cases were included in the study. 63.2% of VSCC were p16-ve/p53abn (HPV-independent (p53abn)) molecular subtype, 29.8% p16+ve/p53wt (HPV-associated) and 1.4% p16-ve/p53wt (HPV-independent (p53wt)) tumors. All diagnostic biopsies (N = 57) showed at least a weak Trop2 expression. Moderate and strong expression was seen in 15/17 (88.2%) of the p16-ve/p53abn, 32/36 (88.8%) of the p16+ve/p53wt and 3/4 (75%) of the p16-ve/p53wt molecular subtype. Expression was significantly higher, as assessed by H score, in the HPV-associated VSCC, compared to HPV-independent.
Conclusion:
VSCCs have high expression of Trop2 and represents a promising therapeutic target. Clinical trials exploring Trop2-directed ADCs such as SG are warranted in this rare cancer type, including in the prognostically poor HPV-independent VSCC with a TP53-mutation (p16-ve/p53abn molecular subtype). The targetable molecule, Trop2, can be easily assessed by immunohistochemistry on diagnostic biopsies from VSCC.
Insights
Vulvar squamous cell carcinomas (VSCCs) show high Trop2 expression, a promising target for antibody-drug conjugates (ADCs). Further clinical trials are recommended for this rare cancer, especially for HPV-independent subtypes.
Area of Science:
- Oncology
- Translational Research
- Molecular Pathology
Background:
- Antibody-drug conjugates (ADCs) show promise in solid tumor treatment.
- Sacituzumab-Govitecan (SG), an anti-Trop2 ADC, is approved for metastatic triple-negative breast cancer.
- Trop2 overexpression in various cancers suggests broader ADC applicability.
Purpose of the Study:
- To investigate Trop2 expression in vulvar squamous cell carcinomas (VSCCs).
- To correlate Trop2 expression with the molecular subtypes of VSCC.
- To assess the potential of Trop2-targeted therapies in VSCC.
Main Methods:
- Immunohistochemistry was used to evaluate Trop2 expression on 57 VSCC diagnostic biopsies.
- An immunoreactive score quantified Trop2 staining intensity.
- Trop2 expression levels were compared across different molecular subtypes of VSCC.
Main Results:
- All VSCC samples (N=57) exhibited at least weak Trop2 expression.
- High Trop2 expression (moderate to strong) was observed in over 88% of HPV-associated and HPV-independent subtypes.
- Trop2 expression, measured by H score, was significantly higher in HPV-associated VSCC compared to HPV-independent subtypes.
Conclusions:
- Vulvar squamous cell carcinomas (VSCCs) demonstrate high Trop2 expression, identifying it as a viable therapeutic target.
- Trop2-directed ADCs, such as Sacituzumab-Govitecan (SG), warrant clinical investigation in VSCC.
- Immunohistochemistry can reliably assess Trop2 expression on diagnostic VSCC biopsies for patient selection.
