Evaluation of HER2 and Nectin-4 Expression in Primary Vaginal Cancers

This study assessed the prevalence and clinical relevance of p16^INK4a, p53, HER2, and Nectin-4 protein expression in primary vaginal cancer (PVC), with HER2 and Nectin-4 representing potentially druggable targets. A total of 34 patients with PVC from the University Medical Center Mainz biobank were included. Immunohistochemistry was used to evaluate the expression of p16, p53, HER2, and Nectin-4: p16, p53, and HER2 staining results were dichotomized (positive vs. negative; mutant vs. wildtype staining pattern), whereas Nectin-4 expression was assessed using an immunoreactive score (IRS) based on staining intensity and the proportion of positive tumor cells. Univariate analyses were performed to identify intergroup differences, and survival analyses were conducted using the log-rank test. Negative p16 expression was significantly associated with adenocarcinomatous histology (p = 0.0211), but neither p16 nor p53 status showed prognostic relevance. HER2 positivity was detected in 14.7% of tumors and was significantly associated with adenocarcinoma (p = 0.0001), p16 negativity (p = 0.0035), and younger age (p = 0.0483). Based on IRS, strong total Nectin-4 expression was observed in 20.59% and moderate membranous Nectin-4 expression in 17.65% of cases. No significant associations were found between HER2 or Nectin-4 expression and clinical outcomes; however, a limited statistical power of the survival analysis due to the low number of events (n = 10 deaths) should be considered. This analysis demonstrates a notable prevalence of HER2 and Nectin-4 expression in PVC.