title: Molecular profile of urothelial carcinoma of the upper urinary tract: are pelvicalyceal and ureteral tumors different?
abstract: OBJECTIVE
  To assess the potential biologic impact of tumor location on oncological outcomes for patients with upper tract urothelial carcinoma (UTUC), we used prospectively collected molecular signatures of high-grade UTUC.
  
  
  METHODS
  Immunohistochemical staining for p21, p27, p53, cyclin E, and Ki-67 was prospectively performed on 96 UTUC specimens of patients with non-metastatic high-grade UTUC treated with extirpative surgery. Patients were grouped according to primary tumor location (pelvicalyceal vs. ureteral) where primary tumor was defined as the highest tumor stage and diameter. Primary outcome was assessment of differences in marker expression between groups. Secondary outcome was difference in survival according to marker status.
  
  
  RESULTS
  Pelvicalyceal and ureteral tumors were found in 52.1 and 47.9 %, respectively, and 42.7 % of patients had non-organ-confined disease. Over a median follow-up of 22.0 months, 31.2 and 20.8 % of patients experienced disease recurrence and died of UTUC, respectively. The total number of altered markers stained for was 0-2 in 67.7 and 3-5 in 32.3 % of patients. The number of altered markers and alteration status of markers were not significantly different between patients with primary pelvicalyceal versus ureteral tumors when stratified by tumor stage and nodal status. There were no significant differences in survival outcomes between both groups when stratified by number of altered markers (0-2 and 3-5).
  
  
  CONCLUSIONS
  The prospective assessment of selected cell cycle and proliferative markers suggests no molecular difference between UTUC of the pelvicalyceal system and that of the ureter. Our study is limited by its size and definition of location.
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA. lauramaria.krabbe@ukmuenster.de.|Department of Urology, University of Muenster Medical Center, Albert-Schweitzer Campus 1, GB A1, 48149, Muenster, Germany. lauramaria.krabbe@ukmuenster.de.
authors.forename: Laura-Maria
authors.initials: LM
authors.lastname: Krabbe
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Aditya
authors.initials: A
authors.lastname: Bagrodia
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Westerman
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Bishoy A
authors.initials: BA
authors.lastname: Gayed
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Ahmed Q
authors.initials: AQ
authors.lastname: Haddad
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Sagalowsky
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.|Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Payal
authors.initials: P
authors.lastname: Kapur
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D019927:Cyclin E / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D007670:Kidney Calices; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D007682:Kidney Pelvis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009392:Nephrectomy; D011379:Prognosis; D011446:Prospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014513:Ureter / Q000601:surgery; D014516:Ureteral Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
chemical_list: C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019394:Ki-67 Antigen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: Comparison; Molecular markers; Upper urinary tract; Urothelial carcinoma