Altered Expression of the Transcription Factor Forkhead Box A1 (FOXA1) Is Associated With Poor Prognosis in Urothelial Carcinoma of the Upper Urinary Tract

Jay D. Raman, Joshua I. Warrick, Carla Caruso, Zhaohai Yang, Lauren Shuman, Richard D. Bruggeman, Shahrokh Shariat, Jose A. Karam, Christopher Wood, Alon Z. Weizer, Mesut Remzi, Andrea Haitel, Karim Bensalah, Nathalie Rioux-Leclerq, Christian Bolenz, Marco Roscigno, Laura Maria Krabbe, Payal Kapur, Yair Lotan, Vitaly Margulis & 1 others David J. DeGraff

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Abstract

Objective To determine the prognostic significance of Forkhead Box A1 (FOXA1) expression in patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Materials and Methods A retrospective analysis of 566 patients undergoing RNU at seven academic medical centers was performed. Tissue microarrays were subjected to immunohistochemistry using a commercially available polyclonal FOXA1 antibody. Logistic regression determined the association of FOXA1 expression with pathologic features and survival outcomes. Results Three hundred twenty-two men and 244 women were included. The pathologic distribution of specimens included 53% muscle-invasive or greater (≥pT2), 74% high-grade, 16% with flat architecture, 13% with necrosis, 21% with lymphovascular invasion, 18% with concomitant carcinoma in situ, and 8% with positive lymph nodes. The median FOXA1 score was 5.0 (range: 0-8). Lower FOXA1 expression was significantly correlated with advanced pathologic stage (≥pT3) (P = .02), concomitant carcinoma in situ (P = .006), and renal pelvis (vs ureter) location (P < .0001). At a median follow-up of 27.0 months (range: 3-196), 139 patients (25%) experienced disease recurrence and 121 (21%) died from the disease. In a multivariate model, lower FOXA1 expression was independently associated with disease recurrence (hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 1.05-1.62, P = .04), cancer-specific mortality (HR: 1.17, 95% CI: 1.03-1.92, P = .04), and all-cause mortality (HR: 1.08, 95% CI: 1.02-1.18, P = .05). Conclusion Lower FOXA1 expression is associated with adverse pathologic features and inferior survival outcomes for UTUC patients undergoing RNU. These data indicate lower FOXA1 expression may be a marker of aggressive disease in UTUC.

Original languageEnglish (US)
Pages (from-to)314.e1-314.e7
JournalUrology
Volume94
DOIs
StatePublished - Aug 1 2016

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Forkhead Transcription Factors
Urinary Tract
Carcinoma
Carcinoma in Situ
Confidence Intervals
Recurrence
Kidney Pelvis
Survival
Mortality
Ureter
Necrosis
Logistic Models
Lymph Nodes
Immunohistochemistry
Muscles
Antibodies
Neoplasms

ASJC Scopus subject areas

  • Urology

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Altered Expression of the Transcription Factor Forkhead Box A1 (FOXA1) Is Associated With Poor Prognosis in Urothelial Carcinoma of the Upper Urinary Tract. / Raman, Jay D.; Warrick, Joshua I.; Caruso, Carla; Yang, Zhaohai; Shuman, Lauren; Bruggeman, Richard D.; Shariat, Shahrokh; Karam, Jose A.; Wood, Christopher; Weizer, Alon Z.; Remzi, Mesut; Haitel, Andrea; Bensalah, Karim; Rioux-Leclerq, Nathalie; Bolenz, Christian; Roscigno, Marco; Krabbe, Laura Maria; Kapur, Payal; Lotan, Yair; Margulis, Vitaly; DeGraff, David J.

In: Urology, Vol. 94, 01.08.2016, p. 314.e1-314.e7.

Research output: Contribution to journalArticle

Raman, JD, Warrick, JI, Caruso, C, Yang, Z, Shuman, L, Bruggeman, RD, Shariat, S, Karam, JA, Wood, C, Weizer, AZ, Remzi, M, Haitel, A, Bensalah, K, Rioux-Leclerq, N, Bolenz, C, Roscigno, M, Krabbe, LM, Kapur, P, Lotan, Y, Margulis, V & DeGraff, DJ 2016, 'Altered Expression of the Transcription Factor Forkhead Box A1 (FOXA1) Is Associated With Poor Prognosis in Urothelial Carcinoma of the Upper Urinary Tract', Urology, vol. 94, pp. 314.e1-314.e7. https://doi.org/10.1016/j.urology.2016.05.030
Raman, Jay D. ; Warrick, Joshua I. ; Caruso, Carla ; Yang, Zhaohai ; Shuman, Lauren ; Bruggeman, Richard D. ; Shariat, Shahrokh ; Karam, Jose A. ; Wood, Christopher ; Weizer, Alon Z. ; Remzi, Mesut ; Haitel, Andrea ; Bensalah, Karim ; Rioux-Leclerq, Nathalie ; Bolenz, Christian ; Roscigno, Marco ; Krabbe, Laura Maria ; Kapur, Payal ; Lotan, Yair ; Margulis, Vitaly ; DeGraff, David J. / Altered Expression of the Transcription Factor Forkhead Box A1 (FOXA1) Is Associated With Poor Prognosis in Urothelial Carcinoma of the Upper Urinary Tract. In: Urology. 2016 ; Vol. 94. pp. 314.e1-314.e7.
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title = "Altered Expression of the Transcription Factor Forkhead Box A1 (FOXA1) Is Associated With Poor Prognosis in Urothelial Carcinoma of the Upper Urinary Tract",
abstract = "Objective To determine the prognostic significance of Forkhead Box A1 (FOXA1) expression in patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Materials and Methods A retrospective analysis of 566 patients undergoing RNU at seven academic medical centers was performed. Tissue microarrays were subjected to immunohistochemistry using a commercially available polyclonal FOXA1 antibody. Logistic regression determined the association of FOXA1 expression with pathologic features and survival outcomes. Results Three hundred twenty-two men and 244 women were included. The pathologic distribution of specimens included 53{\%} muscle-invasive or greater (≥pT2), 74{\%} high-grade, 16{\%} with flat architecture, 13{\%} with necrosis, 21{\%} with lymphovascular invasion, 18{\%} with concomitant carcinoma in situ, and 8{\%} with positive lymph nodes. The median FOXA1 score was 5.0 (range: 0-8). Lower FOXA1 expression was significantly correlated with advanced pathologic stage (≥pT3) (P = .02), concomitant carcinoma in situ (P = .006), and renal pelvis (vs ureter) location (P < .0001). At a median follow-up of 27.0 months (range: 3-196), 139 patients (25{\%}) experienced disease recurrence and 121 (21{\%}) died from the disease. In a multivariate model, lower FOXA1 expression was independently associated with disease recurrence (hazard ratio [HR]: 1.11, 95{\%} confidence interval [CI]: 1.05-1.62, P = .04), cancer-specific mortality (HR: 1.17, 95{\%} CI: 1.03-1.92, P = .04), and all-cause mortality (HR: 1.08, 95{\%} CI: 1.02-1.18, P = .05). Conclusion Lower FOXA1 expression is associated with adverse pathologic features and inferior survival outcomes for UTUC patients undergoing RNU. These data indicate lower FOXA1 expression may be a marker of aggressive disease in UTUC.",
author = "Raman, {Jay D.} and Warrick, {Joshua I.} and Carla Caruso and Zhaohai Yang and Lauren Shuman and Bruggeman, {Richard D.} and Shahrokh Shariat and Karam, {Jose A.} and Christopher Wood and Weizer, {Alon Z.} and Mesut Remzi and Andrea Haitel and Karim Bensalah and Nathalie Rioux-Leclerq and Christian Bolenz and Marco Roscigno and Krabbe, {Laura Maria} and Payal Kapur and Yair Lotan and Vitaly Margulis and DeGraff, {David J.}",
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T1 - Altered Expression of the Transcription Factor Forkhead Box A1 (FOXA1) Is Associated With Poor Prognosis in Urothelial Carcinoma of the Upper Urinary Tract

AU - Raman, Jay D.

AU - Warrick, Joshua I.

AU - Caruso, Carla

AU - Yang, Zhaohai

AU - Shuman, Lauren

AU - Bruggeman, Richard D.

AU - Shariat, Shahrokh

AU - Karam, Jose A.

AU - Wood, Christopher

AU - Weizer, Alon Z.

AU - Remzi, Mesut

AU - Haitel, Andrea

AU - Bensalah, Karim

AU - Rioux-Leclerq, Nathalie

AU - Bolenz, Christian

AU - Roscigno, Marco

AU - Krabbe, Laura Maria

AU - Kapur, Payal

AU - Lotan, Yair

AU - Margulis, Vitaly

AU - DeGraff, David J.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Objective To determine the prognostic significance of Forkhead Box A1 (FOXA1) expression in patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Materials and Methods A retrospective analysis of 566 patients undergoing RNU at seven academic medical centers was performed. Tissue microarrays were subjected to immunohistochemistry using a commercially available polyclonal FOXA1 antibody. Logistic regression determined the association of FOXA1 expression with pathologic features and survival outcomes. Results Three hundred twenty-two men and 244 women were included. The pathologic distribution of specimens included 53% muscle-invasive or greater (≥pT2), 74% high-grade, 16% with flat architecture, 13% with necrosis, 21% with lymphovascular invasion, 18% with concomitant carcinoma in situ, and 8% with positive lymph nodes. The median FOXA1 score was 5.0 (range: 0-8). Lower FOXA1 expression was significantly correlated with advanced pathologic stage (≥pT3) (P = .02), concomitant carcinoma in situ (P = .006), and renal pelvis (vs ureter) location (P < .0001). At a median follow-up of 27.0 months (range: 3-196), 139 patients (25%) experienced disease recurrence and 121 (21%) died from the disease. In a multivariate model, lower FOXA1 expression was independently associated with disease recurrence (hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 1.05-1.62, P = .04), cancer-specific mortality (HR: 1.17, 95% CI: 1.03-1.92, P = .04), and all-cause mortality (HR: 1.08, 95% CI: 1.02-1.18, P = .05). Conclusion Lower FOXA1 expression is associated with adverse pathologic features and inferior survival outcomes for UTUC patients undergoing RNU. These data indicate lower FOXA1 expression may be a marker of aggressive disease in UTUC.

AB - Objective To determine the prognostic significance of Forkhead Box A1 (FOXA1) expression in patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Materials and Methods A retrospective analysis of 566 patients undergoing RNU at seven academic medical centers was performed. Tissue microarrays were subjected to immunohistochemistry using a commercially available polyclonal FOXA1 antibody. Logistic regression determined the association of FOXA1 expression with pathologic features and survival outcomes. Results Three hundred twenty-two men and 244 women were included. The pathologic distribution of specimens included 53% muscle-invasive or greater (≥pT2), 74% high-grade, 16% with flat architecture, 13% with necrosis, 21% with lymphovascular invasion, 18% with concomitant carcinoma in situ, and 8% with positive lymph nodes. The median FOXA1 score was 5.0 (range: 0-8). Lower FOXA1 expression was significantly correlated with advanced pathologic stage (≥pT3) (P = .02), concomitant carcinoma in situ (P = .006), and renal pelvis (vs ureter) location (P < .0001). At a median follow-up of 27.0 months (range: 3-196), 139 patients (25%) experienced disease recurrence and 121 (21%) died from the disease. In a multivariate model, lower FOXA1 expression was independently associated with disease recurrence (hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 1.05-1.62, P = .04), cancer-specific mortality (HR: 1.17, 95% CI: 1.03-1.92, P = .04), and all-cause mortality (HR: 1.08, 95% CI: 1.02-1.18, P = .05). Conclusion Lower FOXA1 expression is associated with adverse pathologic features and inferior survival outcomes for UTUC patients undergoing RNU. These data indicate lower FOXA1 expression may be a marker of aggressive disease in UTUC.

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