Immunohistochemical expression of ErbB/HER family proteins in patients with vulvar cancer

Objective To investigate the immunohistochemical (IHC) expression of the ErbB/HER family in primary vulvar squamous cell carcinoma (VSCC). Methods We analyzed a series of 125 patients who were surgically treated for VSCC from January 1980 to June 2016. All cases had lymph node (LN) staging and 80 had LN metastasis. A tissue microarray was built for epidermal growth factor receptor (EGFR), HER2, HER3, and HER4 IHC staining. Results In the primary tumor we found positive expressions for EGFR, HER2, HER3, and HER4 in 5%, 0.9%, 0.9%, and 22.8%, respectively. For the LN metastasis, expressions of EGFR and HER4 were positive in 22.2% and 39.1%, respectively. No cases had positive staining for HER2 and HER3 in the LN metastasis. For HER4, positive expression correlated with smaller tumor sizes (P = 0.02). However, positive HER4 was related to adverse prognostic factors such as: histological grade (P = 0.012), presence of lymphovascular space invasion (40.9% vs 16.2%; P = 0.035), and perineural invasion (57.1% vs 16.7%; P = 0.006). Notably, all cases with LN metastasis had positive HER4 in the primary tumor (P < 0.001). ErbB/HER family expression was not related to worse survival. Conclusion EGFR, HER2, and HER3 were infrequently expressed in VSCC by IHC. HER4 IHC expression was found in 22.8% of cases and was related to adverse prognostic factors.