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. 2023 Sep;149(11):8235-8241.
doi: 10.1007/s00432-023-04761-8. Epub 2023 Apr 17.

TROP-2 is widely expressed in vulvar squamous cell carcinoma and represents a potential new therapeutic target

Mateja Condic  1 , Eva K Egger  1 , Niklas Klümper  2 , Glen Kristiansen  3 , Alexander Mustea  1 , Thore Thiesler #  3 , Damian J Ralser #  4
Affiliations

TROP-2 is widely expressed in vulvar squamous cell carcinoma and represents a potential new therapeutic target

Mateja Condic et al. J Cancer Res Clin Oncol. 2023 Sep.

Abstract

Purpose: Vulvar squamous cell carcinoma (VSCC) is a rare malignancy of the female genital tract with increasing incidence rates. Etiologically, HPV-dependent and HPV-independent VSCC are distinguished. Surgical treatment and/or radiotherapy represent the therapeutic mainstay for localized disease. For recurrent or metastatic VSCC, treatment options are limited. Research has identified trophoblast cell surface antigen 2 (TROP-2) to be broadly expressed across different tumor entities. The aim of the present study was to systematically investigate the expression of TROP-2 in VSCC.

Methods: TROP-2 protein expression was investigated by immunohistochemistry in a cohort comprising n = 103 patients with primary VSCC. A four-tier scoring system (0: no staining, 1 + : low staining, 2 + : moderate staining, 3 + : high staining) was applied for quantification of protein expression. For further analyses, two groups (low TROP-2 expression: 0/1 + ; high TROP-2 expression: 2 + /3 +) were generated. The entire study cohort, as well as HPV-dependent and HPV-independent VSCC were considered separately.

Results: In the entire VSCC study cohort, TROP-2 expression was present in 97.1% of all cases (n = 100) with 74.8% displaying high TROP-2 expression (2 + /3 +). Only 2.9% of tumors showed absent TROP-2 expression. Of note, all HPV-dependent VSCC (n = 18) demonstrated high TROP-2 expression (2 + /3 +). In the subgroup of HPV-independent VSCC (n = 70), high TROP-2 expression was associated with favorable clinical outcomes based on log rank test and univariate cox analysis.

Conclusion: TROP-2 protein expression is of prognostic value in HPV-independent VSCC. The broad expression of TROP-2 in VSCC indicates the TROP-2 directed ADC Sacituzumab govitecan as a potential new therapeutic strategy for VSCC patients.

Keywords: Antibody-drug conjugate; HPV; TROP-2; Vulvar squamous cell carcinoma.

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Conflict of interest statement

The authors declare that there are no conflicts of interests.

Figures

Fig. 1
Fig. 1
Representative histology sections showing absent (0; A), low (1 + ; B), moderate (2 + , C), and high (3 + , D) TROP-2 protein expression. (E) Pie charts illustrating the distribution of expression intensities in the entire VSCC cohort, the HPV-independent VSCC cohort, and the HPV-dependent VSCC cohort. Bar graphs showing differentiation into low (0, 1 +) and high (2, 3 +) TROP-2 protein expression. Scale bar = 60 µm
Fig. 2
Fig. 2
Kaplan–Meier estimates show a trend towards a shorter overall survival (OS; p = 0.058) in patients with low expression of TROP-2 in the entire VSCC cohort (A). In HPV-independent VSCC, high TROP-2 expression was linked to favorable OS (p = 0.048; B). P-values for the group comparison (low vs., high expression) are based on log-rank tests, significance threshold p < 0.5
See this image and copyright information in PMC

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