Exploring Nectin-4 expression in hepatocellular carcinoma.

632 Background: Nectin cell adhesion protein 4 (Nectin-4) is overexpressed in various malignancies, contributing to cancer progression and poor prognosis. We aimed to assess Nectin-4 expression in hepatocellular carcinoma (HCC). Methods: Patients who underwent primary liver tumor resection for HCC upon initial diagnosis at National Taiwan University Hospital in 2019 were included. Exclusion criteria consisted of prior systemic or loco-regional therapy, or death within three months post-surgery. Immunohistochemical (IHC) staining for Nectin-4 (EPR15613-68, Abcam) was conducted and independently reviewed by two pathologists. Nectin-4 expression patterns (membranous, cytoplasmic, and nuclear) and intensity were scored on a 0–3 scale, with normal eccrine glands (2+) serving as a positive control. Nectin-4 expression was further assessed in primary and paired progressive or metastatic tissue samples from patients with available paired samples. Results: Of the 193 patients, 175 had specimens available for IHC analysis. Nectin-4 expression was detected in 22.9% of these patients, with intensity scores of 0 in 77.1%, 1 in 22.3%, and 2 in 0.6%. The majority of staining pattern was cytoplasmic (94.3%), with membranous staining observed in 5.1% of cases. Nectin-4 expression was significantly associated with higher pathological grades ( p = 0.005) but showed no correlation with recurrence-free survival ( p = 0.771) or overall survival ( p = 0.396) after surgery. Importantly, Nectin-4 expression intensity significantly increased in paired progressive or metastatic samples compared to initial HCC specimens ( p = 0.046; n = 27). Conclusions: Nectin-4 expression is associated with higher pathological grades but not related to clinical outcomes in HCC. Increased Nectin-4 expression in progressive or metastatic disease highlights its potential as a therapeutic target.