Immunohistochemical analysis of estrogen receptors in prostate and clinical correlation in men with benign prostatic hyperplasia

Abstract

Purpose: Estrogens act through interaction with 2 receptor subtypes, ER alpha (ERα) and ER beta (ERβ), in human prostate. The aim of the present study was to semiquantitatively assess the differential expression of ER subtypes in human benign prostatic hyperplasia (BPH) by use of immunocytochemistry (IHC) methods and to explore their relationship with various measures of BPH.

Materials and methods: A total of 45 patients with BPH undergoing transurethral resection of the prostate and 22 patients with bladder cancer with normal prostate undergoing surveillance cystoscopy were studied as cases and controls, respectively. Quantitative immunolabeling of ER subtypes was scored by use of a semiquantitative scale. Also, correlations were assessed between ER levels in prostate and various measures of BPH.

Results: Overall, we found strong immunostaining for ERα in stroma and for ERβ in epithelium, respectively. The IHC score for ERα differed significantly between BPH patients and controls in both stroma (p≤0.001) and epithelium (p=0.008), respectively. The ERβ IHC score was also significantly higher in the epithelium of BPH patients (p=0.01). Also, we found a significant correlation between prostatic ER levels and various clinical measures of BPH.

Conclusions: ERs may play an important role in the pathogenesis of BPH.

Keywords: Antibodies; Estrogens; Immunohistochemistry; Prostate.

Fig. 1. Positive controls for estrogen receptors (ERs). Breast cancer tissue for ER alpha (A) and hypothalamus tissue sections for ER beta (B) were taken as positive controls (H&E, ×40).

Fig. 2. Immunohistochemical analysis of estrogen receptor (ER) subtypes and Ki-67 expression in prostatic specimens from benign prostatic hyperplasia (BPH) patients (A, C, E, G) and controls (B, D, F, H). (A) Section from BPH specimens shows positive immunostaining (red arrow) for ER beta (ERβ) (H&E, ×40). (B) Representative area from normal prostate shows absence of ERβ immunostaining (H&E, ×40). (C) Intense ERβ positivity was primarily localized to epithelial nuclei (black pointer) in BPH tissues, whereas (D) nuclear staining was sparse (blue arrow) and seen mostly in epithelium of normal prostates (C, D: H&E, ×400). (E) In BPH specimens, immunoreactivity for ER alpha (ERα) was intensely expressed in both epithelial and stromal compartments. Note the close proximity between immunoreactive epithelial and stromal cells (black pointer and yellow arrow) (H&E, ×400). (F) ERα was expressed with much lower intensity in both stromal and epithelial compartments in controls (H&E, ×400). (G) Abundant nuclear staining for Ki-67 (yellow arrow) was found in BPH specimens, whereas (H) a representative area from normal prostate shows absent staining (G, H: H&E, ×400).

Fig. 3. Comparison of immunocytochemistry (IHC) scores of both estrogen receptor (ER) subtypes in benign prostatic hyperplasia (BPH) patients vs. normal controls. ^*Significant difference (p<0.05).

Fig. 4. Significant correlation between various measures of benign prostatic hyperplasia (BPH) and estrogen receptor (ER) in prostatic stroma and epithelium. (A) ER alpha (ERα) in stroma vs. age (r=0.37). (B) ERα in stroma vs. prostate-specific antigen (PSA) (r=0.32). (C) ERα in epithelium vs. International Prostate Symptom Score (IPSS) (r=0.32). (D) ERα in epithelium vs. prostate size (r=0.38). (E) ERα in stroma vs. prostate size (r=0.51). (F) ERα in epithelium vs. serum estradiol (r=0.53). (G) ER beta (ERβ) in epithelium vs. serum estradiol (r=0.56). A p-value of <0.05 was considered statistically significant.