Trop2-Expression in Correlation to the Molecular Subtype in Vulvar Squamous Cell Carcinomas (VSCC).

Abstract

Targeted therapy with antibody-drug conjugates (ADCs) has shown promising results in the treatment of various solid tumours. Sacituzumab-govitecan (SG), a humanised anti-Trop2 monoclonal antibody in combination with the cytotoxic topoisomerase I inhibitor SN38, has been approved for the treatment of metastatic triple-negative breast cancer. The treatment approach with SG requires the expression of Trop2 in the tumour cells. Trop2 is overexpressed in many other cancers, suggesting a broader therapeutic application of these ADCs beyond breast cancer. We are investigating the expression of Trop2 in vulvar squamous cell carcinoma (VSCC) and how this relates to molecular classification. Immunohistochemical Trop2 expression was assessed in diagnostic biopsies of VSCC using an immunoreactive score. The staining results were compared with the molecular subtype of VSCC. 57 cases were included in the study. 63.2% of VSCC were 16-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 weak Trop2-expression. Expression was significantly higher, as assessed by an immunreactive score, in the HPV-associated VSCC, compared to HPV-independent. VSCC have high expression of Trop2 and represents a promising therapeutic target. Clinical trials exploring Trop2 directed ADCs such as Sacituzumab-Govitecan 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. ree version).