ArticleFrontiers in oncology2026
Immunohistochemistry-based risk stratification of upper tract urothelial carcinoma.
Article in Frontiers in oncology, 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
Background: Upper tract urothelial carcinoma (UTUC) is characterized by significant biological heterogeneity. Although high-throughput sequencing has unveiled the genomic landscape of UTUC, its routine clinical application is hindered by high costs and technical complexity. This study aimed to develop a cost-effective molecular subtyping strategy using immunohistochemistry (IHC) as surrogate markers and to construct a novel risk stratification model integrating driver genes ( Methods: We retrospectively analyzed 215 patients with UTUC who underwent radical nephroureterectomy between 2021 and 2024. IHC staining was performed for GATA3, CK20, CK5/6, CD44, P53, and FGFR3. Tumors were initially stratified into Luminal-like or Basal-like subtypes. Subsequently, a three-tier "RiskGroup" stratification was constructed: Low Risk (Luminal-like with wild-type P53), Intermediate Risk (Luminal-like with aberrant P53), and High Risk (Basal-like). A prognostic nomogram was developed based on multivariate Cox regression analysis and validated using the Concordance Index (C-index) and Decision Curve Analysis (DCA). Results: Luminal-like and basal-like subtypes showed distinct clinicopathologic profiles. RiskGroup further captured heterogeneity, with increasing Ki-67 across low-, intermediate-, and high-risk groups (median 30%, 60%, 60%; P<0.001). The intermediate-risk group, despite luminal immunophenotype, was enriched for high-grade disease (94.2%) and had worse RFS than the low-risk group. RFS differed across RiskGroup (P<0.001); the high-risk group had the poorest outcomes and remained independently associated with RFS (HR 2.60, 95% CI 1.27-5.33; P = 0.009), whereas intermediate risk was not significant after adjustment (HR 1.63; P = 0.227). RiskGroup, pathological T stage, and lymphovascular invasion were independent prognostic factors. The nomogram showed good discrimination (C-index 0.769) and 1-year RFS AUC 0.823 with net clinical benefit. Conclusion: This IHC-based, biologically informed stratification identifies an occult aggressive subset within luminal tumors and complements routine pathology. The internally validated nomogram is exploratory given cohort composition and lack of external validation; multicenter validation is warranted.
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