ArticleVirchows Archiv : an international journal of pathology2026
Stage-dependent prognostic impact of GATA3/FOXA1-defined luminal-like subtype in upper tract urothelial carcinoma.
Article in Virchows Archiv : an international journal of pathology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Upper tract urothelial carcinoma (UTUC) exhibits poorly defined molecular heterogeneity and lacks reliable biomarkers for subtype classification. We investigated the prognostic impact of luminal-like UTUC defined by GATA3 and FOXA1 immunohistochemistry in 245 surgically resected UTUC cases. The cohort included 183 non-muscle-invasive (NMI) and 62 muscle-invasive (MI) tumors. The Kaplan-Meier and Cox analyses demonstrated that the luminal-like subtype had opposite prognostic implications depending on muscle invasiveness: poorer outcomes in NMI-UTUC but more favorable outcomes in MI-UTUC. To provide biological context, we additionally analyzed independent RNA-seq datasets stratified by GATA3 and FOXA1 expression. Luminal-like tumors showed consistent upregulation of cell growth and developmental pathways, whereas non-luminal-like tumors, particularly in MI cases, were enriched for immune-related signatures such as antigen presentation and T-cell recruitment. Exploratory biomarker screening also identified one luminal-like gene and three non-luminal-like genes with survival implications. Using a large cohort of patients with UTUC, we establish GATA3 and FOXA1 as robust surrogate IHC biomarkers for luminal-like UTUC. Their prognostic value is dependent on muscle invasiveness, with transcriptomic analyses providing complementary mechanistic insights.
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