Clinical study of steroid receptors in nonmuscle invasive bladder cancer: A domain worth revisiting

Abstract

Introduction: The prognostic significance of steroid receptors in bladder cancer remains controversial. This study was designed to determine the expression status of androgen receptor (AR), estrogen receptors (ERα and Erβ), and its potential role in predicting survival in patients with nonmuscle invasive bladder cancer (NMIBC).

Methods: Sixty patients of NMIBC were screened and 57 (41 males and 16 females) were included in our study. The tissue microarray slides were evaluated by pathologists blinded to the clinical information. Association of distribution of steroid receptors with stage, grade, progression, and recurrence was seen.

Results: The mean age of the population was 60.9 ± 9.3 years. Pathologically, majority of the patients were Ta (Ta: T1 stage 61.4% vs. 38.6%). Nine (15.8%) of the tumors stained positive for AR while one (1.8%) tumor stained positive for ERα and 36 (63.2%) tumors stained for ERβ. A higher proportion of male NMIBC stained positive for AR (19.5% vs. 6.2%, P = 0.420) while ERβ positivity was higher in females (58.5% vs. and 75%,P = 0.247). AR-negative tumors showed higher recurrence (20/48%-42%) as compared to AR-positive tumors (2/9%-22%). ERβ-positive tumors showed higher recurrence (15/36%-42% vs. 7/21%-33%, P = 0.179). Progression-free survival (PFS) was found to be significantly lower for ERβ-negative group (log-rank test P = 0.035).

Conclusion: AR and ERβ positivity is found in NMIBC patients while ERα shows minimal staining in NMIBC patients. Although it did not reach a statistical significance, a higher proportion of AR-negative and ERβ-positive tumors recurred as compared to AR-positive and ERβ-negative patients. PFS was significantly lower in ERβ-negative group. Further exploratory studies on larger sample sizes are required to validate these findings in NMIBC patients.

Figure 1

Tissue microarray showing immunohistochemistry staining of low-grade urothelial carcinoma showing nuclear positivity of androgen receptor of weak intensity. Magnification in (a) ×100, (b) ×200, (c) ERα of mild intensity (×200), (d) ERβ of moderate intensity, (e) ×400, (f) ×100