title: Expression of steroid hormone receptors and its prognostic significance in urothelial carcinoma of the upper urinary tract.
abstract: To assess the expression status of steroid hormone receptors in upper urinary tract urothelial carcinoma (UUTUC), we immunohistochemically stained for androgen receptor (AR), estrogen receptor-α (ERα), ERβ, glucocorticoid receptor (GR), and progesterone receptor (PR) in 99 UUTUC specimens and paired non-neoplastic urothelial tissues. AR/ERα/ERβ/GR/PR was positive in 20%/18%/62%/63%/16% of tumors, which was significantly lower (except PR) than in benign urothelial tissues [57% (P < 0.001)/40% (P = 0.001)/85% (P = 0.001)/84% (P = 0.002)/13% (P = 0.489)]. There were no significant associations between each receptor expression pattern and histopathological characteristic of the tumors including tumor grade/stage. Kaplan-Meier and log-rank tests revealed no significant prognostic value of each receptor expression in these 99 patients. However, patients with UUTUC positive for either ERα or PR had a significantly higher risk of disease-specific mortality (P = 0.025), compared with those with UUTUC negative for both. PR positivity alone in pT3 or pT4 tumors was also strongly associated with the risk of disease-specific mortality (P = 0.040). Multivariate analysis further identified the expression of ERα and/or PR as a strong predictor for disease-specific mortality in the entire cohort of the patients (hazard ratio, 2.434; P = 0.037). Thus, in accordance with previous observations in bladder specimens, significant decreases in the expression of AR/ERα/ERβ/GR in UUTUC, compared with that in non-neoplastic urothelium, were observed. Meanwhile, the negativity of both ERα and PR in UUTUC as well as the negativity of PR alone in deeply invasive tumor was suggested to serve as a prognosticator.
authors.affiliation: a Department of Pathology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.|b Department of Urology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kashiwagi
authors.affiliation: c Department of Urology , Osaka University Graduate School of Medicine , Suita , Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Fujita
authors.affiliation: d Department of Urology , Osaka General Medical Center , Osaka , Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: e Department of Pathology , Osaka General Medical Center , Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fushimi
authors.affiliation: a Department of Pathology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.|b Department of Urology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ide
authors.affiliation: a Department of Pathology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.|b Department of Urology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.|f Department of Pathology & Laboratory Medicine , University of Rochester Medical Center , Rochester , NY , USA.|g Wilmot Cancer Institute, University of Rochester Medical Center , Rochester , NY , USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.affiliation: a Department of Pathology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.|b Department of Urology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.|f Department of Pathology & Laboratory Medicine , University of Rochester Medical Center , Rochester , NY , USA.|g Wilmot Cancer Institute, University of Rochester Medical Center , Rochester , NY , USA.
authors.forename: Taichi
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: a Department of Pathology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.|b Department of Urology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.forename: Leonardo O
authors.initials: LO
authors.lastname: Reis
authors.affiliation: a Department of Pathology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.affiliation: a Department of Pathology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.|b Department of Urology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
authors.affiliation: c Department of Urology , Osaka University Graduate School of Medicine , Suita , Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
authors.affiliation: a Department of Pathology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.|b Department of Urology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.|f Department of Pathology & Laboratory Medicine , University of Rochester Medical Center , Rochester , NY , USA.|g Wilmot Cancer Institute, University of Rochester Medical Center , Rochester , NY , USA.|h Department of Urology , University of Rochester Medical Center , Rochester , NY , USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyamoto
mesh_terms: D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011944:Receptors, Androgen / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis*; D011980:Receptors, Progesterone / Q000096:biosynthesis*; D014571:Urologic Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone
keywords: Androgen receptor; estrogen receptor; glucocorticoid receptor; immunohistochemistry; progesterone receptor; prognosis; upper urinary tract urothelial carcinoma