TROP2 expression in gastric and GEJ adenocarcinomas: associations with clinicopathological features, biomarkers, and treatment outcomes

Background Trophoblast cell surface antigen 2 (TROP2) is frequently expressed in solid tumors, including gastric cancer (GC) and gastroesophageal junction cancer (GEJC), but its distribution and clinical relevance remain unclear. Patients and methods We analyzed patients with GC/GEJC who underwent prospective multibiomarker testing. TROP2 expression was assessed by immunohistochemistry using multiple cut-offs and associations with clinicopathological features, biomarkers, and outcomes were evaluated. Results Among 272 patients (169 with metastatic cancer), TROP2 expression was observed in 87%, 79%, and 62% at ≥25%, ≥50%, and ≥75% cut-offs, respectively. Higher cut-offs were associated with higher proportions of male patients, gastroesophageal junction tumors, intestinal-type histology, and liver metastasis. Among patients with TROP2-high tumors (>75% positivity), positivity rates in the full cohort were 17.8% for human epidermal growth factor receptor 2, 50.9% for claudin 18.2, 4.7% for deficient mismatch repair, and 30.2% for a programmed death-ligand 1 combined positive score >10; in the metastatic cohort, the corresponding rates were 18.6%, 48.0%, 5.9%, and 35.3%, respectively. Overall, 38.8% of TROP2-high patients in the full cohort and 31.3% in the metastatic cohort were negative for all four biomarkers. TROP2 expression was not associated with treatment outcomes for first-line platinum-based doublet chemotherapy or second-line taxane-based chemotherapy. Conclusions TROP2 is widely expressed in GC/GEJC irrespective of stage. Higher expression thresholds delineate distinct clinicopathological features without prognostic impact. Its broad prevalence extends to patients lacking actionable biomarkers, supporting its potential as a therapeutic target.