ESMO gastrointestinal oncology · 2026
TROP2 expression in gastric and GEJ adenocarcinomas: associations with clinicopathological features, biomarkers, and treatment outcomes.
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Tong Y, Nakayama I, Sakamoto N, Miyashita Y, Shiba Y, Hirotaka U, Sugawara Y, Okemoto D, Yamamoto K, Seguchi K, Ogura T, Matsubara Y, Hashimoto T, Mishima S, Kotani D, Kawazoe A, Kuboki Y, Bando H, Kojima T, Yoshino T, Shitara K
Аннотация
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.
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.