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Trop2-expression in primary vulvar squamous cell carcinoma
Frederik A Stuebs1, Antje Knöll2, Arndt Hartmann3
1Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), Bavarian Cancer Research Center (BZKF), Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitaetsstrasse 21-23, 91054 Erlangen, Germany.
Objectives:
Vulvar squamous cell carcinoma (VSCC) is a rare malignant disease but with increasing incidence. Therapeutic options are generally limited to surgery and radio-(chemo)therapy. New strategies for therapy are lacking. Trophoblast cell surface antigen 2 (Trop2) is a new target being used in different tumor entities. The purpose of the current research is to assess the expression of Trop2 in VSCC.
Methods:
We constructed a next generation tissue micro array (ngTMA) including women with primary VSCC treated between 2000 and 2021 at the Department of Gynecology and Obstetrics, Erlangen University Hospital analyzing the expression of Trop2. Further clinicopathologic characteristics were analyzed: tumor stage, regional lymph node-status, venous-, lymphatic- and perineural sheath invasion, depth of invasion, grading, p16/p53 subtype and tumor infiltration lymphocytes.
Results:
A total of 217 women were included. Trop2 was expressed in 100 % of VSCC. Women were split in two groups, the "low expression" and the "high expression" groups, according to the median of Trop2 (H-score: 279). p16+/p53- is the most common p16/p53 subtype in patients with high Trop2 expression. Trop2 favored a better prognosis in women with VSCC, hence not clinically impactful for the most common p16-/p53+ subtype.
Conclusion:
The ubiquitous expression of Trop2 makes it an interesting potential target for the Trop2 directed antibody drug conjugate (ADC) sacituzumab govitecan (SG). Clinical trials evaluating the safety and effectiveness of SG in VSCC are needed.
Insights
Trophoblast cell surface antigen 2 (Trop2) is expressed in all vulvar squamous cell carcinoma (VSCC) cases, suggesting it as a potential therapeutic target. Further clinical trials are needed to evaluate Trop2-targeted therapies for VSCC.
Area of Science:
- Gynecologic Oncology
- Cancer Biomarkers
- Translational Research
Background:
- Vulvar squamous cell carcinoma (VSCC) incidence is rising, with limited therapeutic options beyond surgery and radio(chemo)therapy.
- Trophoblast cell surface antigen 2 (Trop2) is an emerging therapeutic target in various cancers.
- Novel treatment strategies for VSCC are urgently needed.
Purpose of the Study:
- To assess the expression of Trop2 in VSCC.
- To investigate the correlation between Trop2 expression and clinicopathologic features in VSCC.
- To evaluate Trop2 as a potential therapeutic target in VSCC.
Main Methods:
- A next-generation tissue microarray (ngTMA) was constructed from 217 VSCC patient samples treated between 2000 and 2021.
- Trop2 expression was analyzed, alongside clinicopathologic characteristics including tumor stage, lymph node status, invasion patterns, grading, and p16/p53 subtypes.
- Patients were stratified into "low" and "high" Trop2 expression groups based on the median H-score.
Main Results:
- Trop2 expression was ubiquitous, detected in 100% of VSCC cases.
- High Trop2 expression was associated with the p16+/p53- subtype.
- Trop2 expression indicated a better prognosis in VSCC, though its impact varied by p16/p53 subtype.
Conclusions:
- The universal expression of Trop2 in VSCC positions it as a promising target for Trop2-directed antibody-drug conjugates (ADCs) like sacituzumab govitecan (SG).
- Clinical trials are warranted to determine the safety and efficacy of sacituzumab govitecan for treating VSCC.
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