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

Autor: Raman JD; Penn State Milton S. Hershey Medical Center, Hershey, PA., Warrick JI; Penn State Milton S. Hershey Medical Center, Hershey, PA., Caruso C; Penn State Milton S. Hershey Medical Center, Hershey, PA., Yang Z; Penn State Milton S. Hershey Medical Center, Hershey, PA., Shuman L; Penn State Milton S. Hershey Medical Center, Hershey, PA., Bruggeman RD; Penn State Milton S. Hershey Medical Center, Hershey, PA., Shariat S; General Hospital, Medical University of Vienna, Vienna, Austria., Karam JA; M.D. Anderson Cancer Center, Houston, TX., Wood C; M.D. Anderson Cancer Center, Houston, TX., Weizer AZ; University of Michigan, Ann Arbor, MI., Remzi M; General Hospital, Medical University of Vienna, Vienna, Austria., Haitel A; General Hospital, Medical University of Vienna, Vienna, Austria., Bensalah K; University of Rennes, Rennes, France., Rioux-Leclerq N; University of Rennes, Rennes, France., Bolenz C; University of Ulm, Ulm, Germany., Roscigno M; AO Papa Giovanni XXIII, Bergamo, Italy., Krabbe LM; UT Southwestern Medical Center, Dallas, TX., Kapur P; UT Southwestern Medical Center, Dallas, TX., Lotan Y; UT Southwestern Medical Center, Dallas, TX., Margulis V; UT Southwestern Medical Center, Dallas, TX., DeGraff DJ; Penn State Milton S. Hershey Medical Center, Hershey, PA. Electronic address: ddegraff@hmc.psu.edu.
Jazyk: angličtina
Zdroj: Urology [Urology] 2016 Aug; Vol. 94, pp. 314.e1-7. Date of Electronic Publication: 2016 May 20.
DOI: 10.1016/j.urology.2016.05.030
Abstrakt: 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.
(Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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