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

Q: How was TROP2 expression evaluated in the UTUC samples?

TROP2 protein expression was assessed in 114 UTUC tissue samples using immunohistochemistry, followed by RNA-seq–based in silico analyses.

Q: What clinicopathological features were associated with high TROP2 expression?

High TROP2 expression was associated with papillary morphology, low tumor grade, early pathologic T stage, and favorable clinical outcomes.

Q: Does TROP2 expression have prognostic value beyond standard clinicopathological factors?

Yes. High TROP2 expression was identified as an independent prognostic factor and correlated with improved prognosis.

Sep 22, 2026

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Study examines whether TROP2 protein expression in upper tract urothelial carcinoma (UTUC) is clinically meaningful for prognosis and molecular characterization. Immunohistochemistry quantified TROP2 in 114 UTUC tissue samples, and RNA-seq–based in silico analyses further assessed TACSTD2 expression patterns. Results show TROP2 restricted mainly to tumor tissues, with overexpression linked to papillary morphology, low grade, early pathologic T stage, and improved outcomes. High TROP2 acts as an independent prognostic factor and correlates with UPK3 and Nectin-4.

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World Journal of Urology (2026) 44:166 [https://doi.org/10.1007/s00345-026-06250-2](https://doi.org/10.1007/s00345-026-06250-2) RESEARCH TROP2 expression is associated with early stage and favorable prognosis in upper tract urothelial carcinoma Go Kobayashi1 · Yohei Sekino2 · Tetsutaro Hayashi2 · Hikaru Nakahara3 · Kohei Kobatake2 · Hiroyuki Kitano2 · Keisuke Goto2 · Hiroaki Niitsu3 · Takao Hinoi3 · Kazuhiro Sentani1 · Nobuyuki Hinata2 Received: 28 September 2025 / Accepted: 1 February 2026 © The Author(s) 2026 Abstract 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 oflower 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. Keywords TROP2 · Nectin-4 · Upper tract urothelial carcinoma · Clinicopathological significance · Immunohistochemistry 􀀍 Yohei Sekino [akikosekino@gmail.com](akikosekino@gmail.com) 1 Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan 2 Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan 3 Department of Clinical and Molecular Genetics, Hiroshima University Hospital, Hiroshima, Japan Introduction Urothelial carcinoma (UC) is a common malignancy, with bladder UC (BLCA) constituting the predominant subtype. In contrast, upper tract UC (UTUC) is uncommon, accounting for approximately 5–10% of all urothelial cancers [1] . Despite advances in diagnostic techniques and surgical management, the survival outcomes of UTUC patients remain poor, with 5-year cancer-specific survival (CSS) < 50% for pT2/pT3 tumors [2] . Accordingly, reliable prognostic markers are needed to improve risk stratification and guide therapy. Clinicopathological parameters such as pathological stage, tumor grade, and morphological subtype are widely accepted as prognostic indicators [1, 3]; however, their predictive power is limited by interpatient heterogeneity. Recently, increasing attention has been directed toward 1 3 molecular and immunohistochemical biomarkers with potential prognostic and therapeutic implications in UTUC [4–11], yet clinically applicable markers remain lacking. The transmembrane protein TROP2, encoded by the TACSTD2 gene, is a cell surface glycoprotein involved in calcium signaling and oncog

FAQs

How was TROP2 expression evaluated in the UTUC samples?

TROP2 protein expression was assessed in 114 UTUC tissue samples using immunohistochemistry, followed by RNA-seq–based in silico analyses.

What clinicopathological features were associated with high TROP2 expression?

High TROP2 expression was associated with papillary morphology, low tumor grade, early pathologic T stage, and favorable clinical outcomes.

Does TROP2 expression have prognostic value beyond standard clinicopathological factors?

Yes. High TROP2 expression was identified as an independent prognostic factor and correlated with improved prognosis.

Sep 22, 2026

Upload by Ezra