Nectin-4 expression in vulvar squamous cell carcinoma

Therapy options for women with vulvar squamous cell carcinoma (VSCC) are limited. New strategies such as immune checkpoint inhibitors (ICI) or antibody-drug conjugates (ADC) are lacking. One potential target for the ADC Enfortumab Vedotin (EV) is Nectin-4. EV has been successfully used to treat metastatic urothelial carcinoma (mUC). Currently, there is limited data on the expression of Nectin-4 for VSCC. Our aim was therefore to investigate the expression of Nectin-4 in women with VSCC. In total, 219 formalin-fixed paraffin-embedded tissue (FFPE) samples of primary VSCC were collected between 2000 and 2021. A next generation tissue microarray (ngTMA) was constructed. The assessment of Nectin-4 expression was performed through the implementation of immunohistochemistry (IHC). We also performed NECTIN-4 fluorescence in situ hybridization (FISH) to evaluate amplification of Nectin-4. The median Nectin-4 H-score for membranous expression was 22.5, with 32.4% of VSCCs exhibiting moderate to strong expression. We could not show that Nectin-4 H-score (membranous) significantly influenced overall survival in addition to other prognostic factors. The rates of regional lymph node metastases, lymphatic vascular space involvement, G3-Grading, perineural sheath invasion and p16-/p53+ were highest in Nectin-4-negative VSCC. 28.8% of recurrent VSCC had moderate or strong expression of Nectin-4. None of the investigated VSCC (primary or recurrent) showed amplification of Nectin-4 in contrast to mUC. Nectin-4 could be a potential target in the therapy of women with VSCC. Further (pre-)clinical data is needed to evaluate the use of EV in therapy of women with VSCC.