Prospective comparison of molecular signatures in urothelial cancer of the bladder and the upper urinary tract--is there evidence for discordant biology?
OBJECTIVE
Upper tract urothelial carcinoma is rare and less well studied than bladder cancer. It remains questionable if findings in bladder cancer can safely be extrapolated to upper tract urothelial carcinoma. We prospectively evaluate molecular profiles of upper tract urothelial carcinoma and bladder cancer using a cell cycle biomarker panel.


METHODS
Immunohistochemical staining for p21, p27, p53, cyclin E and Ki-67 was prospectively performed for 96 patients with upper tract urothelial carcinoma and 159 patients with bladder cancer with nonmetastatic high grade urothelial carcinoma treated with extirpative surgery. Data were compared between the groups according to pathological stage. Primary outcome was assessment of differences in marker expression. Secondary outcome was difference in survival according to marker status.


RESULTS
During a median followup of 22.0 months 31.2% of patients with upper tract urothelial carcinoma and 28.3% of patients with bladder cancer had disease recurrence, and 20.8% and 27.7% died of upper tract urothelial carcinoma and bladder cancer, respectively. The number of altered markers was not significantly different between the study groups. Overall 34 patients (35.4%) with upper tract urothelial carcinoma and 62 (39.0%) with bladder cancer had an unfavorable marker score (more than 2 markers altered). There were no significant differences between upper tract urothelial carcinoma and bladder cancer in the alteration status of markers, the number of altered markers and biomarker score when substratified by pathological stage. There were no significant differences in survival outcomes between patients with upper tract urothelial carcinoma and those with bladder cancer according to the number of altered markers and biomarker score.


CONCLUSIONS
Our results demonstrate the molecular similarity of upper tract urothelial carcinoma and bladder cancer in terms of cell cycle and proliferative tissue markers. These findings have important implications and support the further extrapolation of treatment paradigms established in bladder cancer to upper tract urothelial carcinoma.
Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Urology, University of Muenster Medical Center, Muenster, Germany.
Laura-Maria
LM
Krabbe
Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
Yair
Y
Lotan
Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
Aditya
A
Bagrodia
Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
Bishoy A
BA
Gayed
Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
Oussama M
OM
Darwish
Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
Ramy F
RF
Youssef
Department of Urology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany.
Christian
C
Bolenz
Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
Arthur I
AI
Sagalowsky
Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
Ganesh V
GV
Raj
Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
Shahrokh F
SF
Shariat
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.
Payal
P
Kapur
Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: Vitaly.margulis@utsouthwestern.edu.
Vitaly
V
Margulis
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D011446:Prospective Studies; D014516:Ureteral Neoplasms / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
biological markers; carcinoma; transitional cell; urinary bladder neoplasms