Prospective Comparison of Molecular Signatures in Urothelial Cancer of the Bladder and the Upper Urinary Tract—Is There Evidence for Discordant Biology?

• Published in: The Journal of urology Vol. 191; no. 4; pp. 926 - 931
• Main Authors: Krabbe, Laura-Maria, Lotan, Yair, Bagrodia, Aditya, Gayed, Bishoy A, Darwish, Oussama M, Youssef, Ramy F, Bolenz, Christian, Sagalowsky, Arthur I, Raj, Ganesh V, Shariat, Shahrokh F, Kapur, Payal, Margulis, Vitaly
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2014; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; biological markers; carcinoma; Carcinoma, Transitional Cell - genetics; Female; Humans; Kidney Neoplasms - genetics; Male; Medical sciences; Middle Aged; Molecular Diagnostic Techniques; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Nephrology. Urinary tract diseases; Prospective Studies; transitional cell; Tumors; Tumors of the urinary system; Ureteral Neoplasms - genetics; urinary bladder neoplasms; Urinary Bladder Neoplasms - genetics; Urinary tract. Prostate gland; Urology; BC; CSS; cancer specific survival; LND; MS; lymph node dissection; UTUC; upper tract urothelial carcinoma; UC; biomarker score; RC; urothelial carcinoma; lymphovascular invasion; carcinoma; recurrence-free survival; radical nephroureterectomy; biological markers; RNU; urinary bladder neoplasms; radical cystectomy; LVI; RFS; transitional cell; urothelial carcinoma of the bladder; Urothelial cancer; Nephrology; Urinary system disease; Carcinoma; Biological marker; Biology; Urinary tract disease; Malignant tumor; Gene expression; Bladder tumor; Urology; Prospective; Urinary system; Urinary bladder; Upper urinary tract; Bladder disease; Comparative study; Cancer
• ISSN: 0022-5347; 1527-3792
• DOI: 10.1016/j.juro.2013.09.031

Purpose 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. Materials and 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.