SAT-319 Steroids and Endocrine Disruptors in Prostate Cancer Tissue

Abstract Disclosure: J. Vitku: None. T. Skodova: None. L. Gadus: None. L. Kolatorova: None. J. Heracek: None. Background: Prostate cancer (Pca) is a hormone-dependent disease in which steroid hormones play a key role in its pathogenesis. However, prostate steroid pathways remain poorly understood, with research focusing mainly on androgens. Additionally, endocrine disruptors (EDs)—substances that interfere with steroid hormone action— may influence Pca, but their presence and role in its pathogenesis remain unknown.Aim of the study: The study aimed to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for analyzing the steroids and EDs in prostate tissue and to apply it to samples from 42 patients who underwent robotic radical prostatectomy for localized Pca. Three samples were analyzed per patient: one from cancerous tissue and two from non-cancerous tissue in the peripheral and transitional zones. Methods: Two sensitive LC-MS/MS methods were developed. The first method enables the analysis of 20 compounds, including 3 estrogens, 7 bisphenols, 5 parabens, oxybenzone, nonylphenol, and 3 phytoestrogens. The second method allows for the analysis of 22 steroids, including corticosteroids and androgens. The key advantage of these methods is a single sample preparation, followed by analysis using two LC-MS/MS methods.Results: Both conjugated and unconjugated fractions were analyzed. Among steroid hormones, the most abundant in the unconjugated form were cortisol, pregnenolone, and dehydroepiandrosterone (DHEA), with concentrations of 2.45±0.52 pg/mg, 2.42±0.11 pg/mg, and 2.27±0.19 pg/mg of tissue, respectively. In the conjugated form, the most abundant were pregnenolone (870.65±25.92 pg/mg), DHEA (125.73±5.53 pg/mg), and androstenedione (5.37±0.16 pg/mg).Among EDs, the most prevalent in the unconjugated form were propylparaben (PP; 4.53±1.19 pg/mg), methylparaben (MP; 3.89±0.83 pg/mg), bisphenol S (BPS; 1.34±0.12 pg/mg), and bisphenol A (BPA; 1.19±0.11 pg/mg). In the conjugated form, the highest levels were found for MP (123.97±9.84 pg/mg), PP (7.94±1.00 pg/mg), BPA (2.89±0.29 pg/mg), and BPS (1.15±0.10 pg/mg).Notably, levels of unconjugated BPA and BPS, as well as conjugated BPS, were significantly higher (p < 0.05) in cancerous tissue compared to non-cancerous tissues (peripheral or transitional zones). Conversely, conjugated MP and ethylparaben were significantly lower in cancerous tissue compared to non-cancerous tissue from the transitional zone.Conclusion: These results confirm the presence of EDs in the prostate and suggest that bisphenols may accumulate in cancerous tissue. A key finding is that ED levels in the prostate are comparable to those of endogenous hormones, potentially disrupting steroid pathways. Steroid levels will be further analyzed for correlation with the Gleason score and PSA levels to assess carcinoma aggressiveness and patient prognosis.Acknowledgement: Supported by NU21J-01-00040 of Czech Ministry of Health Presentation: Saturday, July 12, 2025