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-a (ERa), ERb, glucocorticoid receptor (GR), and progesterone receptor (PR) in 99 UUTUC specimens and paired nonneoplastic urothelial tissues. AR/ERa/ERb/GR/PR was positive in 20%/18%/62%/63%/16% of tumors, which was significantly lower (except PR) than in benign urothelial tissues [57% (. 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 ERa or PR had a significantly higher risk of disease-specific mortality (P D 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 D 0.040). Multivariate analysis further identified the expression of ERa and/or PR as a strong predictor for disease-specific mortality in the entire cohort of the patients (hazard ratio, 2.434; P D 0.037). Thus, in accordance with previous observations in bladder specimens, significant decreases in the expression of AR/ERa/ERb/GR in UUTUC, compared with that in non-neoplastic urothelium, were observed. Meanwhile, the negativity of both ERa and PR in UUTUC as well as the negativity of PR alone in deeply invasive tumor was suggested to serve as a prognosticator.

ZKSCAN3 expression in urothelial carcinoma of the upper urinary tract and its impact on patient outcomes

“…Indeed, a similar tendency was seen in the expression of androgen receptor (i.e. 42% in bladder tumors [10] vs. 28% in ureteral tumors [8] vs. 11% in renal pelvic tumors [8]) as well as another transcription factor GATA3 (i.e. 86% in bladder tumors [11] vs. 68% in ureteral tumors [12] vs. 36% in renal pelvic tumors [12]) we stained using the same protocol with identical antibodies.…”

“…Immunohistochemical staining was performed on the sections (5 µm thick) from the UUTUC TMA, using a primary antibody to ZKSCAN3 (TA308508; dilution 1:50; OriGene), as we described previously [6,8]. All the stains were manually scored by a single pathologist (H.M.) who was blinded to sample identity.…”

Histopathological and prognostic significance of the expression of sex hormone receptors in bladder cancer: A meta-analysis of immunohistochemical studies

“…IHC has detected AR protein signals in 13–55% of bladder or upper urinary tract urothelial tumors [19, 20, 36, 38–44, 49–51], which is significantly lower than the positive rates in normal/non-neoplastic urothelial tissues (58–86%) reported by most of respective comparative studies [36, 38, 40, 51]. However, at least three immunohistochemical studies have demonstrated no AR expression in normal urothelium [42, 43, 52].…”

“…However, at least three immunohistochemical studies have demonstrated no AR expression in normal urothelium [42, 43, 52]. Significant or insignificant down-regulation of AR expression in high-grade or MI urothelial carcinomas, compared with low-grade or NMI tumors, has also been found [19, 36, 38–40, 42, 44, 49–51]. However, several studies showed even slight increases in AR positivity in high-grade and/or MI tumors [20, 41, 51].…”

“…Significant or insignificant down-regulation of AR expression in high-grade or MI urothelial carcinomas, compared with low-grade or NMI tumors, has also been found [19, 36, 38–40, 42, 44, 49–51]. However, several studies showed even slight increases in AR positivity in high-grade and/or MI tumors [20, 41, 51]. Furthermore, two studies each have suggested a considerable association of AR expression in bladder tumors with a higher risk of the progression of only MI disease [36] or both NMI and MI diseases [43] or a lower risk of the recurrence of NMI disease [42, 44], or no such strong association with the prognosis of patients with NMI or MI disease [40, 41].…”