590 Background: Biliary tract cancers (BTC), including cholangiocarcinoma and gallbladder carcinoma, are aggressive tumors with limited treatment options and poor prognosis. Antibody–drug conjugates (ADCs) targeting membrane proteins, such as claudin-18.2 (CLDN18.2) and trophoblast cell surface antigen 2 (Trop-2), are promising targets for other epithelial cancers. However, their expression patterns and clinical relevance in BTC remain unclear. This study aimed to evaluate CLDN18 and Trop-2 expression levels in BTC and their potential as therapeutic targets. Methods: We retrospectively analyzed 636 BTC patients who underwent surgical resection at Asan Medical Center between February 1998 and October 2020. Immunohistochemistry (IHC) was performed using validated antibodies. CLDN18 positivity was defined as membranous staining in ≥75% of tumor cells with a moderate-to-strong intensity. Trop-2 expression was quantified by H-score and categorized as low (200). Associations with clinicopathologic features and survival outcomes were assessed via Kaplan–Meier and Cox regression analyses. Results: CLDN18 IHC and Trop-2 IHC were evaluated in all 636 cases. CLDN18 was positive for 5.2% of patients. By subtype, positivity was the highest in perihilar cholangiocarcinoma (pCCA, 22.2%), followed by distal CCA (dCCA, 5.6%), gallbladder cancer (GBC, 4.9%), and intrahepatic CCA (iCCA, 1.6%). Trop-2 high and medium expression were observed in 69.5% and 20.1% of patients, respectively; its expression was low in iCCA (27.3%). CLDN18 expression showed adverse clinicopathologic features. The Trop-2 high expression was linked to higher T category and more frequent lymphovascular and perineural invasion. Neither biomarker was significantly associated with OS or DFS. Conclusions: CLDN18.2 was highly expressed in specific BTC subtypes, particularly pCCA and GBC, while Trop-2 was broadly expressed in the entire BTC cohort. These findings supported further clinical development of CLDN18.2- and Trop-2-directed therapies in BTC.
Shin et al. (Sat,) studied this question.