title: Feasibility of obtaining biomarker profiles from endoscopic biopsy specimens in upper tract urothelial carcinoma: preliminary results.
abstract: OBJECTIVE
  To prospectively evaluate the feasibility of obtaining a reliable histochemical assessment of cell cycle biomarkers from endoscopic biopsy specimens of patients with upper tract urothelial cancer.
  
  
  METHODS
  Overall, 17 patients were identified who had an available biopsy as well as those who underwent subsequent radical nephroureterectomy (RNU) or segmental ureterectomy (SU) for clinically localized high-grade upper tract urothelial cancer of the renal pelvis or ureter. Of those 17 patients, 15 (88%) had sufficient tissue to undergo immunohistochemical staining. Biopsies were obtained using various endoscopic techniques. Tumor characteristics were recorded and prospectively evaluated for immunohistochemical expression of 5 biomarkers: p21, p27, p53, cyclin E, and Ki67/pRb. Unfavorable prognostic score (PS) was defined as>2 altered markers.
  
  
  RESULTS
  The median age of the patients was 68 years (range: 53-82y) with 87% being males. Of the 15 specimens, 9 (60%) tumors were organ confined (T≤2 and N0), and all were high grade. Of the 15 patients, 4 (27%), 7 (46.6%), 3 (20%), and 1 (6.7%) individuals had 1, 2, 3, and 5 markers altered on biopsy marker profiling, respectively, with Ki67 being the most frequent alteration (13/15; 87.7%). An overall concordance rate of 60% (9/15) was seen between biopsy and RNU/SU PS. Those patients with favorable biopsy biomarker PS were less likely to display adverse pathological features, with organ-confined disease in 7/11 (63.6%) patients and 9/11 (81.8%) being free of carcinoma in situ in the final specimen. Additionally, 10/11 (91%) had no evidence of necrosis and 7/11 (64%) had no evidence of lymphovascular invasion on final pathologic evaluation.
  
  
  CONCLUSIONS
  Preliminary results suggest that obtaining interpretable biomarker profile of ureteroscopic biopsy specimens is feasible. Tumor heterogeneity and limited biopsy material may account for the discordance between biopsy and RNU/SU specimens. Meaningful biopsy biomarker profiling could serve as a powerful tool for individualizing treatment regimens and augmenting current predictive variables. Further studies are needed to evaluate clinical applicability.
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Bishoy A
authors.initials: BA
authors.lastname: Gayed
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Aditya
authors.initials: A
authors.lastname: Bagrodia
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Mansi
authors.initials: M
authors.lastname: Gaitonde
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Laura-Maria
authors.initials: LM
authors.lastname: Krabbe
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Matthew
authors.initials: M
authors.lastname: Meissner
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Payal
authors.initials: P
authors.lastname: Kapur
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Ramy F
authors.initials: RF
authors.lastname: Youssef
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Arthur
authors.initials: A
authors.lastname: Sagalowsky
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address: vitaly.margulis@utsouthwestern.edu.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D015331:Cohort Studies; D004724:Endoscopy / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: Biomarkers; Cell cycle; Upper tract urothelial carcinoma