Heat shock proteins 60 and 70 are associated with long-term outcome of T1-stage high-grade urothelial tumors of the bladder treated with intravesical Bacillus Calmette-Guérin immunotherapy

• Published in: Urologic oncology Vol. 36; no. 12; pp. 531.e9 - 531.e17
• Main Authors: Mano, Roy, Zilber, Sofia, Di Natale, Renzo G., Kedar, Daniel, Lifshitz, David A., Yossepowitch, Ofer, Baniel, Jack, Margel, David
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2018
• Subjects: Bacillus Calmette-Guérin immunotherapy; Disease progression; Heat shock proteins; Nonmuscle invasive bladder cancer; Urothelial carcinoma; Heat shock proteins; Bacillus Calmette-Guérin immunotherapy; Nonmuscle invasive bladder cancer; Urothelial carcinoma; Disease progression
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2018.09.007

•Heat shock proteins are molecular chaperons that maintain cellular function.•Elevated HSP60 levels predict disease progression in Bacillus Calmette-Guérin treated T1 high-grade bladder tumors.•Decreased HSP70 levels predict disease progression and recurrence in this cohort.•Patients with both predictors all recurred and had an 80% progression rate at follow-up.•Further studies may validate HSP70 and HSP60 as significant predictors for Bacillus Calmette-Guérin failure.
High-grade nonmuscle-invasive urothelial tumors of the bladder that fail intravesical Bacillus Calmette-Guérin (BCG) immunotherapy are at the highest risk of progression. Initial evidence links heat shock protein expression levels and outcome of bladder cancer after BCG treatment.
We aimed to determine the association between HSP60, 70, and 90 expression levels and long-term outcomes of T1 high-grade (T1HG) urothelial bladder tumors treated with BCG immunotherapy.
Data of 54 consecutive patients with primary T1HG bladder tumors who underwent transurethral resection between 2002 and 2008 and received at least an induction course of BCG were reviewed. Immunohistochemical staining for heat shock protein (HSP)60, 70, and 90 were performed on resected specimens.
Study outcomes included disease recurrence and progression. The association between HSP expression levels and outcomes were evaluated with univariable and multivariable Cox proportional hazards models.
During a median follow-up of 9.6 years, 25 patients had a disease recurrence and 14 patients a disease progression. Estimated 5-year recurrence and progression-free survival were 59% and 81%, respectively.
On multivariable analyses, HSP60 staining >65% was associated with a higher risk for progression (hazard ratio [HR] = 3.96, 95% confidence interval [CI] 1.35–11.58, P = 0.012), and HSP70 staining >5% was associated with a decreased risk for progression (HR = 0.33, 95% CI 0.11–0.98, P = 0.045), and recurrence (HR = 0.29, 95% CI 0.13–0.65, P = 0.003). HSP90 expression was not associated with disease recurrence or progression. Five patients had both a HSP60 staining >65% and a HSP70 staining ≤5% all of whom recurred at a median time of 6 months (interquartile range 3, 16) and 80% of whom progressed at a median time of 26 months (interquartile range 5, 60).
HSP60 and 70 cellular expression levels are associated with long-term outcome following BCG treatment of T1HG urothelial bladder tumors. These findings, if further validated, may be used to better stratify the risk of disease recurrence and progression in this group of patients.