Abstract 26P
Background
AR and ER play important roles in various processes in prostate. However, the role of androgens, estrogens and their receptors in regulating CSC phenotype in PCa is controversial. The study assessed characteristics of AR and ER alpha (ERα) and beta (ERβ) subtypes expression in association with CSC markers CD133 and CD44.
Methods
56 radical prostatectomy specimens were studied. Double immunofluorescence was used to stain ERα and ERβ, AR, CD133 and CD44 on consecutive slides. Staining was assessed semiquantitatively. AR and ER were evaluated separately in tumor epithelium and stroma in 3-15 random non-crossing high power fields (HPF, x400) per case with calculation of total staining score (TSS) by multiplication of scores for proportion of stained nuclei and intensity. For CD133 only presence of staining was analyzed, and for CD44 – staining intensity.
Results
Median (interquartile range) TSS for CD133+ (65.4%) and CD133- (34.6%) cases for different receptors are shown in the table. Table: 26P
CD133+ | CD133- | pMann-Whitney | |
AR | 1.64 (1.2-3.0) | 3.0 (2.0-4.6) | 0.025 |
ERα epith | 0.5 (0.1-1.0) | 0.5 (0.17-1.10) | 0.91 |
ERα stroma | 1.0 (0.57-1.82) | 1.4 (0.6-2.33) | 0.63 |
ERβ epith | 5.7 (1.88-7.0) | 4.8 (2.5-6.71) | 0.74 |
ERβ stroma | 3.67 (2.0-6.0) | 3.71 (1.1-6.5) | 0.65 |
AR appeared to be lower in CD133+ cases, that possibly means that lower AR levels and less dependence on androgen signaling may lead to CSC phenotype. No significant correlations were found between CD44 intensity and all AR and ER characteristics (pSpearman>0.05). Correlations between AR and ERs levels were assessed separately in CD133+ and CD133- cases. Stromal ERα and ERβ; ERβ in stroma and epithelium were significantly correlated in both groups, but correlation between ERα and ERβ in epithelium was seen only in CD133+ cases (r=0.49, pSpearman<0.05), so possibly presence of both receptors in PCa cells is important for the development of CSC features as a result of hormonal stimulation.
Conclusions
Levels of AR were lower in CD133+ PCa, and in these cases also correlation between ER subtypes in cancer cells was found. This may assume that CSC features are obtained in PCa that is less sensitive to androgens, but responsive to estrogens, and relative levels of ERα and ERβ are important.
Editorial acknowledgement
Clinical trial identification
Legal entity responsible for the study
M. Puchinskaya.
Funding
Belarusian Republican Foundation for Fundamental Research, grants No. M14M-143, M19M-123.
Disclosure
M. Puchinskaya: Financial Interests, Personal, Invited Speaker: Roche.
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