Prognostic impact of TROP2 in adenocarcinoma of the esophageal junction and stomach

INTRODUCTION: Adenocarcinoma of the esophageal junction and stomach (AEG/S) remains one of the deadliest cancers worldwide. New treatment options are urgently needed. A new target could be trophoblast cell surface protein 2 (TROP2), which is expressed in a variety of solid tumors and can be targeted, e.g., by sacituzumab govitecan, which has shown promising results in triple-negative breast cancer. This study investigates the expression of TROP2 in patients with AEG/S and correlates its expression with clinical and histopathological endpoints. METHODS: TROP2 expression was assessed in a cohort of 250 patients who underwent primary surgery for AEG/S. Immunohistochemistry was performed on tissue microarrays constructed from primary tumors and lymph node metastases to quantify TROP2 expression intensity. Clinical variables, including overall survival and patient demographics, as well as tumor-specific characteristics such as stage and grade, were correlated with TROP2 expression to evaluate its potential prognostic relevance in AEG/S. RESULTS: TROP2 was expressed in 86% of primary tumors and 81.3% of lymph node metastases. The intensity of TROP2 expression (low vs. medium vs. high) was correlated negatively with overall survival (p < 0.05, 70.9 months vs. 54.2 months vs. 39.5 months), lymphatic invasion (p = 0.05, V = 0.138), and higher grading (p = 0.037, V = 0.143). The intensity of TROP2 expression in lymph node metastases and primary tumors correlated significantly (p < 0.001, ρ = 0.444). There was a non-significant increase in positive lymphonodal status (p = 0.093, V = 0.138) in patients with higher TROP2 expression. CONCLUSION: In Caucasian AEG/S patients, TROP2 is expressed in the majority of cases. TROP2 expression intensity itself has an impact on survival, which could be explained by a more aggressive phenotype, which leads to lymphatic invasion and lymph node metastasis.