HSP90β as a potential prognostic biomarker in urothelial carcinoma: insights from NF-κB, IL-8, and heat-shock protein...

Urothelial carcinoma (UC) is a common malignancy with high recurrence rates and limited prognostic markers. Inflammation and stress-response pathways are implicated in tumor progression, with NF-κB, interleukin-8 (IL-8), and heat shock proteins (HSP90α/β) playing key roles in survival signaling and treatment resistance. We evaluated the expression of these proteins in UC and assessed their associations with clinicopathological features.

Formalin-fixed, paraffin-embedded samples from 102 UC patients (168 tumor sections) and 23 controls were analyzed by immunohistochemistry for NF-κB, IL-8, HSP90α, and HSP90β. Expression was semi-quantitatively scored using the immunoreactive score (IRS) and correlated with clinicopathological features using non-parametric tests.

Nuclear NF-κB expression was significantly higher in UC compared with normal urothelium and correlated with tumor stage and nodal involvement. IL-8 was expressed in 53.6% of tumors and 48.8% of adjacent infiltrates but showed no association with grade, stage, or lymph node status; a weak positive correlation with inflammatory infiltrate was observed. Both HSP90 isoforms were upregulated in UC relative to controls, but only HSP90β correlated with grade, stage, and lymph node status. No significant correlations were found between NF-κB, IL-8, and HSP90 expression.

HSP90β expression shows potential as a prognostic biomarker and therapeutic target in UC. Although NF-κB and IL-8 did not demonstrate consistent prognostic value, their patterns highlight the role of inflammatory signaling in tumor biology. These findings warrant validation in larger, more diverse cohorts and support exploration of HSP90-targeted strategies in UC.