Feasibility of obtaining biomarker profiles from endoscopic biopsy specimens in upper tract urothelial carcinoma: preliminary results

Bishoy A. Gayed, Aditya Bagrodia, Mansi Gaitonde, Laura Maria Krabbe, Matthew Meissner, Payal Kapur, Ramy F. Youssef, Arthur Sagalowsky, Yair Lotan, Vitaly Margulis

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalUrologic Oncology: Seminars and Original Investigations
Volume33
Issue number1
DOIs
StatePublished - Jan 1 2015

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Biomarkers
Carcinoma
Biopsy
Neoplasms
Ureteral Neoplasms
Pelvic Neoplasms
Cyclin E
Kidney Pelvis
Carcinoma in Situ
Cell Cycle
Necrosis
Staining and Labeling

Keywords

  • Biomarkers
  • Cell cycle
  • Upper tract urothelial carcinoma

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

@article{61a165c21bcd429e947ad33e38591539,
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.",
keywords = "Biomarkers, Cell cycle, Upper tract urothelial carcinoma",
author = "Gayed, {Bishoy A.} and Aditya Bagrodia and Mansi Gaitonde and Krabbe, {Laura Maria} and Matthew Meissner and Payal Kapur and Youssef, {Ramy F.} and Arthur Sagalowsky and Yair Lotan and Vitaly Margulis",
year = "2015",
month = "1",
day = "1",
doi = "10.1016/j.urolonc.2014.09.017",
language = "English (US)",
volume = "33",
journal = "Urologic Oncology: Seminars and Original Investigations",
issn = "1078-1439",
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TY - JOUR

T1 - Feasibility of obtaining biomarker profiles from endoscopic biopsy specimens in upper tract urothelial carcinoma

T2 - preliminary results

AU - Gayed, Bishoy A.

AU - Bagrodia, Aditya

AU - Gaitonde, Mansi

AU - Krabbe, Laura Maria

AU - Meissner, Matthew

AU - Kapur, Payal

AU - Youssef, Ramy F.

AU - Sagalowsky, Arthur

AU - Lotan, Yair

AU - Margulis, Vitaly

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - Biomarkers

KW - Cell cycle

KW - Upper tract urothelial carcinoma

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U2 - 10.1016/j.urolonc.2014.09.017

DO - 10.1016/j.urolonc.2014.09.017

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VL - 33

JO - Urologic Oncology: Seminars and Original Investigations

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SN - 1078-1439

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