Expression of antibody-drug conjugate targets in vulvar squamous cell carcinoma

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Purpose: Vulvar squamous cell carcinoma (VSCC) is a rare malignancy of the female genital tract with increasing incidence rates. Surgical treatment and/or radiotherapy represent the therapeutic mainstay for localized disease. For recurrent or metastatic VSCC, treatment options are limited. Recently, the implementation of antibody-drug-conjugates (ADC) have revolutionized therapeutic strategies across diverse cancer entities. However, ADCs are currently not considered as a therapeutic option for VSCC. The aim of the present study was to systematically investigate the expression of ADC targets in VSCC including TROP-2, NECTIN-4, HER2/neu, FOLR1 and TF. Methods: Protein expression of TROP-2, NECTIN-4, HER2/neu, FOLR1 and TF were examined by immunohistochemical staining in n =103 VSCC patients. A four-tier scoring system (0: no staining, 1+: low staining, 2+: moderate staining, 3+: high staining) was applied for quantification of protein expression. Expression data were further analyzed with regard to clinical outcomes. Results: 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. Data on further ADC targets will be presented during the DGGG-congress.

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