Association of molecular subtypes based on GATA3, KRT5, and P16 expression with clinicopathological features and prognosis in upper tract urothelial carcinoma.

OBJECTIVES

This study aimed to classify upper tract urothelial carcinoma (UTUC) using GATA3, KRT5, and P16 immunohistochemistry and to evaluate associations of these molecular subtypes with clinicopathological features and outcomes.

PATIENTS/MATERIALS AND

METHODS

Tissue samples from 102 UTUC patients who underwent radical nephroureterectomy were analyzed. Tumors were classified into genomically unstable (GU), urothelial-like (URO), and basal subtypes based on GATA3, KRT5, and P16 expression. Associations with pathological features, recurrence, and survival were analyzed. Kaplan-Meier and Cox regression analyses were used.

RESULTS

The GU, URO, and basal subtypes accounted for 33%, 45%, and 22% of cases, respectively. Subtype was significantly associated with infiltrative pattern (p = 0.009), perineural invasion (p = 0.016), histological variant (p < 0.001), T stage (p = 0.004), N stage (p = 0.017), and vital status (p = 0.005). The basal subtype showed the poorest prognosis, with 3-year overall survival of 41% vs. 85% for the URO subtype (p < 0.001). Multivariable analysis identified diffuse infiltrative pattern (HR 6.84, P = 0.004), lymphovascular invasion (HR 2.12, p = 0.046), and T4 stage (HR 9.80, p = 0.023) as independent risk factors for overall survival, and diffuse infiltrative pattern (HR 6.37, p = 0.006) and T4 stage (HR 12.6, p = 0.012) for recurrence-free survival.

CONCLUSIONS

IHC-based subtyping using GATA3, KRT5, and P16 is significantly associated with aggressive clinicopathological features in UTUC, with the basal subtype showing poor prognosis in univariate analysis. However, it was not an independent prognostic factor in multivariable analysis. While this exploratory strategy may aid in risk stratification, its clinical utility requires further validation in larger, prospective cohorts.