595 Background: HER2 is an established therapeutic target in breast, gastric, and lung cancers, and trastuzumab deruxtecan (T-DXd), a HER2-targeting antibody–drug conjugate, has shown efficacy across multiple HER2-overexpressing solid tumors. However, advanced hepatocellular carcinoma (HCC) was not included in these studies, and the prevalence of HER2 expression in advanced HCC has not been well characterized. We investigated HER2 expression in advanced HCC tissues to explore the potential feasibility of HER2 as a treatment target. Methods: We retrospectively examined archived pretreatment tumor biopsies from 85 patients with advanced HCC who underwent percutaneous needle biopsy at Chiba University Hospital between April 2019 and September 2024. Formalin-fixed paraffin-embedded samples were analyzed by immunohistochemistry (IHC) using the Dako HercepTest II kit and scored 0–3+. Results: Among 85 patients, median age was 73 years, and 88.2% were male. Etiology was HBV in 17.6%, HCV in 27.1%, and non-B/non-C in 55.3%. At biopsy, 36.7% had macrovascular invasion and 35.3% had distant metastases. Prior to biopsy, 62.4% had received prior treatment: surgery (24.7%), locoregional therapy (37.6%), hepatic arterial infusion chemotherapy (HAIC, 1.2%), or systemic therapy (38.8%). After biopsy, 85.9% received treatment, most commonly systemic therapy (74.1%), followed by HAIC (9.4%). Nine patients underwent repeated biopsy, yielding 94 evaluable samples: HER2 was 0 negative in 86 (91.5%), 1+ negative in 7 (7.4%), 2+ equivocal in 0, and 3+ positive in 1 (1.1%). One patient with HER2 3+ expression exhibited a notable clinical course. During 7-year clinical course he received repeated local therapies, including radiofrequency ablation, microwave ablation, and transarterial chemoembolization. Biopsy #1 showed moderately differentiated HCC with HER2 0. After progression on lenvatinib, biopsy #2 revealed poorly differentiated histology and HER2 3+. Conclusions: Limitations of this study include small sample size and retrospective design. HER2 expression in advanced HCC was rare, suggesting it is unlikely to be a broadly applicable therapeutic target. Nonetheless, a subset of patients may harbor or acquire HER2-positive tumors, and further studies are needed to clarify features associated with HER2 expression. The observed conversion from negative to positive highlights the potential dynamic nature of HER2 in HCC and underscores the need for longitudinal evaluation.
Sawada et al. (Sat,) studied this question.