Ber-EP4 Expression and Staining Patterns in Cutaneous Basal Cell Carcinoma: A Clinicopathological Study From a Vietnamese Cohort

BACKGROUND: Ber-EP4 is an immunohistochemical marker targeting epithelial cell adhesion molecule and is widely applied in the diagnosis of cutaneous basal cell carcinoma (BCC). Although highly sensitive, variability in expression level and staining distribution may complicate interpretation in routine practice. OBJECTIVE: This study aimed to characterize Ber-EP4 expression and staining patterns in cutaneous BCC and to assess their associations with clinicopathological features. MATERIALS AND METHODS: Sixty surgically excised cases of cutaneous BCC were retrospectively analyzed. Ber-EP4 immunohistochemistry was performed using an automated staining platform. Expression was evaluated according to the proportion of positive tumor cells, and staining patterns were classified based on spatial distribution. Associations between Ber-EP4 expression and clinicopathological features were analyzed. RESULTS: All cases demonstrated Ber-EP4 positivity, with a mean percentage of Ber-EP4-positive tumor cells per case of 78.1%. High-level expression was observed in 68.3% of cases. Diffuse staining was the predominant pattern, identified in 85.0% of tumors, while nondiffuse patterns accounted for the remaining 15.0%. Ber-EP4 expression showed no significant associations with most clinicopathological variables; however, ulceration was significantly associated with reduced Ber-EP4 expression (aOR = 12.05; 95% confidence interval, 2.41-60.15; P = 0.002). CONCLUSIONS: Ber-EP4 is a highly sensitive immunohistochemical marker for cutaneous BCC, showing predominantly diffuse expression across diverse clinicohistologic contexts. However, reduced expression in ulcerated tumors and the presence of nondiffuse staining patterns highlight potential diagnostic pitfalls, particularly in superficially sampled lesions. These findings underscore the need for cautious interpretation and integrated histomorphological and immunohistochemical assessment to ensure diagnostic accuracy.