TROP2 expression is associated with early stage and favorable prognosis in upper tract urothelial carcinoma

BACKGROUND: TROP2 has recently emerged as a promising therapeutic target, with the antibody‒drug conjugate sacituzumab govitecan. Nevertheless, its biological and clinical relevance in urothelial carcinoma (UC) has not been fully investigated. METHODS: We evaluated TROP2 protein expression in 114 upper tract UC (UTUC) tissue samples using immunohistochemistry. RNA-seq-based in silico analyses was further performed. RESULTS: TROP2 expression was predominantly restricted to tumor tissues and was observed in 72 of 114 cases (63%). TROP2 overexpression was associated with papillary morphology, low tumor grade, early pathological T stage, and favorable clinical outcome. Notably, high TROP2 expression was identified as an independent prognostic factor. Additionally, TROP2 expression showed positive correlations with both UPK3 and Nectin-4 expression. In silico analyses further supported these findings, showing that TACSTD2 (the gene encoding TROP2) expression was significantly elevated in tumors of lower stage, low grade, papillary morphology, luminal subtype, and FGFR3-mutated cases, and was correlated with improved prognosis when the Hiroshima cohort-derived cutoff was applied. Furthermore, a significant correlation between TACSTD2 and NECTIN4 gene expression was observed. Bioinformatics analysis using RNA-Seq datasets revealed that the TACSTD2 high group was significantly enriched in gene sets related to tumor metabolic reprogramming, whereas TACSTD2-low tumors showed signatures related to extracellular matrix remodeling and epithelial-mesenchymal transition (EMT). CONCLUSIONS: Our findings underscore the clinical significance of TROP2 expression in UTUC and suggest that IHC-based evaluation may contribute to prognostic risk stratification.