Predicting Recurrence and Progression of Noninvasive Papillary Bladder Cancer at Initial Presentation Based on Quantitative Gene Expression Profiles

Marc Birkhahn, Anirban P. Mitra, Anthony J. Williams, Gitte Lam, Wei Ye, Ram Datar, Marija Balic, Susan Groshen, Kenneth E. Steven, Richard J Cote

Research output: Contribution to journalArticle

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Abstract

Background: Currently, tumor grade is the best predictor of outcome at first presentation of noninvasive papillary (Ta) bladder cancer. However, reliable predictors of Ta tumor recurrence and progression for individual patients, which could optimize treatment and follow-up schedules based on specific tumor biology, are yet to be identified. Objective: To identify genes predictive for recurrence and progression in Ta bladder cancer at first presentation using a quantitative, pathway-specific approach. Design, setting, and participants: Retrospective study of patients with Ta G2/3 bladder tumors at initial presentation with three distinct clinical outcomes: absence of recurrence (n = 16), recurrence without progression (n = 16), and progression to carcinoma in situ or invasive disease (n = 16). Measurements: Expressions of 24 genes that feature in relevant pathways that are deregulated in bladder cancer were quantified by real-time polymerase chain reaction on tumor biopsies from the patients at initial presentation. Results and limitations: CCND3 (p = 0.003) and HRAS (p = 0.01) were predictive for recurrence by univariate analysis. In a multivariable model based on CCND3 expression, sensitivity and specificity for recurrence were 97% and 63%, respectively. HRAS (p < 0.001), E2F1 (p = 0.017), BIRC5/Survivin (p = 0.038), and VEGFR2 (p = 0.047) were predictive for progression by univariate analysis. Multivariable analysis based on HRAS, VEGFR2, and VEGF identified progression with 81% sensitivity and 94% specificity. Since this is a small retrospective study using medium-throughput profiling, larger confirmatory studies are needed. Conclusions: Gene expression profiling across relevant cancer pathways appears to be a promising approach for Ta bladder tumor outcome prediction at initial diagnosis. These results could help differentiate between patients who need aggressive versus expectant management.

Original languageEnglish
Pages (from-to)12-20
Number of pages9
JournalEuropean Urology
Volume57
Issue number1
DOIs
StatePublished - Jan 1 2010

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Transcriptome
Urinary Bladder Neoplasms
Recurrence
Neoplasms
Retrospective Studies
Sensitivity and Specificity
Carcinoma in Situ
Gene Expression Profiling
Vascular Endothelial Growth Factor A
Real-Time Polymerase Chain Reaction
Appointments and Schedules
Biopsy
Gene Expression
Genes

Keywords

  • CCND3
  • E2F1
  • First presentation
  • HRAS
  • Noninvasive urothelial carcinoma
  • Progression
  • Recurrence
  • Survivin
  • VEGF
  • VEGFR2

ASJC Scopus subject areas

  • Urology

Cite this

Predicting Recurrence and Progression of Noninvasive Papillary Bladder Cancer at Initial Presentation Based on Quantitative Gene Expression Profiles. / Birkhahn, Marc; Mitra, Anirban P.; Williams, Anthony J.; Lam, Gitte; Ye, Wei; Datar, Ram; Balic, Marija; Groshen, Susan; Steven, Kenneth E.; Cote, Richard J.

In: European Urology, Vol. 57, No. 1, 01.01.2010, p. 12-20.

Research output: Contribution to journalArticle

Birkhahn, Marc ; Mitra, Anirban P. ; Williams, Anthony J. ; Lam, Gitte ; Ye, Wei ; Datar, Ram ; Balic, Marija ; Groshen, Susan ; Steven, Kenneth E. ; Cote, Richard J. / Predicting Recurrence and Progression of Noninvasive Papillary Bladder Cancer at Initial Presentation Based on Quantitative Gene Expression Profiles. In: European Urology. 2010 ; Vol. 57, No. 1. pp. 12-20.
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abstract = "Background: Currently, tumor grade is the best predictor of outcome at first presentation of noninvasive papillary (Ta) bladder cancer. However, reliable predictors of Ta tumor recurrence and progression for individual patients, which could optimize treatment and follow-up schedules based on specific tumor biology, are yet to be identified. Objective: To identify genes predictive for recurrence and progression in Ta bladder cancer at first presentation using a quantitative, pathway-specific approach. Design, setting, and participants: Retrospective study of patients with Ta G2/3 bladder tumors at initial presentation with three distinct clinical outcomes: absence of recurrence (n = 16), recurrence without progression (n = 16), and progression to carcinoma in situ or invasive disease (n = 16). Measurements: Expressions of 24 genes that feature in relevant pathways that are deregulated in bladder cancer were quantified by real-time polymerase chain reaction on tumor biopsies from the patients at initial presentation. Results and limitations: CCND3 (p = 0.003) and HRAS (p = 0.01) were predictive for recurrence by univariate analysis. In a multivariable model based on CCND3 expression, sensitivity and specificity for recurrence were 97{\%} and 63{\%}, respectively. HRAS (p < 0.001), E2F1 (p = 0.017), BIRC5/Survivin (p = 0.038), and VEGFR2 (p = 0.047) were predictive for progression by univariate analysis. Multivariable analysis based on HRAS, VEGFR2, and VEGF identified progression with 81{\%} sensitivity and 94{\%} specificity. Since this is a small retrospective study using medium-throughput profiling, larger confirmatory studies are needed. Conclusions: Gene expression profiling across relevant cancer pathways appears to be a promising approach for Ta bladder tumor outcome prediction at initial diagnosis. These results could help differentiate between patients who need aggressive versus expectant management.",
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T1 - Predicting Recurrence and Progression of Noninvasive Papillary Bladder Cancer at Initial Presentation Based on Quantitative Gene Expression Profiles

AU - Birkhahn, Marc

AU - Mitra, Anirban P.

AU - Williams, Anthony J.

AU - Lam, Gitte

AU - Ye, Wei

AU - Datar, Ram

AU - Balic, Marija

AU - Groshen, Susan

AU - Steven, Kenneth E.

AU - Cote, Richard J

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N2 - Background: Currently, tumor grade is the best predictor of outcome at first presentation of noninvasive papillary (Ta) bladder cancer. However, reliable predictors of Ta tumor recurrence and progression for individual patients, which could optimize treatment and follow-up schedules based on specific tumor biology, are yet to be identified. Objective: To identify genes predictive for recurrence and progression in Ta bladder cancer at first presentation using a quantitative, pathway-specific approach. Design, setting, and participants: Retrospective study of patients with Ta G2/3 bladder tumors at initial presentation with three distinct clinical outcomes: absence of recurrence (n = 16), recurrence without progression (n = 16), and progression to carcinoma in situ or invasive disease (n = 16). Measurements: Expressions of 24 genes that feature in relevant pathways that are deregulated in bladder cancer were quantified by real-time polymerase chain reaction on tumor biopsies from the patients at initial presentation. Results and limitations: CCND3 (p = 0.003) and HRAS (p = 0.01) were predictive for recurrence by univariate analysis. In a multivariable model based on CCND3 expression, sensitivity and specificity for recurrence were 97% and 63%, respectively. HRAS (p < 0.001), E2F1 (p = 0.017), BIRC5/Survivin (p = 0.038), and VEGFR2 (p = 0.047) were predictive for progression by univariate analysis. Multivariable analysis based on HRAS, VEGFR2, and VEGF identified progression with 81% sensitivity and 94% specificity. Since this is a small retrospective study using medium-throughput profiling, larger confirmatory studies are needed. Conclusions: Gene expression profiling across relevant cancer pathways appears to be a promising approach for Ta bladder tumor outcome prediction at initial diagnosis. These results could help differentiate between patients who need aggressive versus expectant management.

AB - Background: Currently, tumor grade is the best predictor of outcome at first presentation of noninvasive papillary (Ta) bladder cancer. However, reliable predictors of Ta tumor recurrence and progression for individual patients, which could optimize treatment and follow-up schedules based on specific tumor biology, are yet to be identified. Objective: To identify genes predictive for recurrence and progression in Ta bladder cancer at first presentation using a quantitative, pathway-specific approach. Design, setting, and participants: Retrospective study of patients with Ta G2/3 bladder tumors at initial presentation with three distinct clinical outcomes: absence of recurrence (n = 16), recurrence without progression (n = 16), and progression to carcinoma in situ or invasive disease (n = 16). Measurements: Expressions of 24 genes that feature in relevant pathways that are deregulated in bladder cancer were quantified by real-time polymerase chain reaction on tumor biopsies from the patients at initial presentation. Results and limitations: CCND3 (p = 0.003) and HRAS (p = 0.01) were predictive for recurrence by univariate analysis. In a multivariable model based on CCND3 expression, sensitivity and specificity for recurrence were 97% and 63%, respectively. HRAS (p < 0.001), E2F1 (p = 0.017), BIRC5/Survivin (p = 0.038), and VEGFR2 (p = 0.047) were predictive for progression by univariate analysis. Multivariable analysis based on HRAS, VEGFR2, and VEGF identified progression with 81% sensitivity and 94% specificity. Since this is a small retrospective study using medium-throughput profiling, larger confirmatory studies are needed. Conclusions: Gene expression profiling across relevant cancer pathways appears to be a promising approach for Ta bladder tumor outcome prediction at initial diagnosis. These results could help differentiate between patients who need aggressive versus expectant management.

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KW - Survivin

KW - VEGF

KW - VEGFR2

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