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).
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Penn State Milton S. Hershey Medical Center, Hershey, PA.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Raman
authors.affiliation: Penn State Milton S. Hershey Medical Center, Hershey, PA.
authors.forename: Joshua I
authors.initials: JI
authors.lastname: Warrick
authors.affiliation: Penn State Milton S. Hershey Medical Center, Hershey, PA.
authors.forename: Carla
authors.initials: C
authors.lastname: Caruso
authors.affiliation: Penn State Milton S. Hershey Medical Center, Hershey, PA.
authors.forename: Zhaohai
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Penn State Milton S. Hershey Medical Center, Hershey, PA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Shuman
authors.affiliation: Penn State Milton S. Hershey Medical Center, Hershey, PA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Bruggeman
authors.affiliation: General Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: Shahrokh
authors.initials: S
authors.lastname: Shariat
authors.affiliation: M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Karam
authors.affiliation: M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Christopher
authors.initials: C
authors.lastname: Wood
authors.affiliation: University of Michigan, Ann Arbor, MI.
authors.forename: Alon Z
authors.initials: AZ
authors.lastname: Weizer
authors.affiliation: General Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: Mesut
authors.initials: M
authors.lastname: Remzi
authors.affiliation: General Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Haitel
authors.affiliation: University of Rennes, Rennes, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Bensalah
authors.affiliation: University of Rennes, Rennes, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rioux-Leclerq
authors.affiliation: University of Ulm, Ulm, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bolenz
authors.affiliation: AO Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Roscigno
authors.affiliation: UT Southwestern Medical Center, Dallas, TX.
authors.forename: Laura-Maria
authors.initials: LM
authors.lastname: Krabbe
authors.affiliation: UT Southwestern Medical Center, Dallas, TX.
authors.forename: Payal
authors.initials: P
authors.lastname: Kapur
authors.affiliation: UT Southwestern Medical Center, Dallas, TX.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.affiliation: UT Southwestern Medical Center, Dallas, TX.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
authors.affiliation: Penn State Milton S. Hershey Medical Center, Hershey, PA. Electronic address: ddegraff@hmc.psu.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: DeGraff
mesh_terms: D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality / Q000601:surgery*; D005260:Female; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000096:biosynthesis*; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D014157:Transcription Factors / Q000096:biosynthesis*; D014513:Ureter / Q000601:surgery*; D014516:Ureteral Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery*
chemical_list: C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D014157:Transcription Factors