Androgen receptor antigen density and S-phase fraction in prostate cancer: a pilot study (original) (raw)
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Plasma Androgen Receptor in Prostate Cancer
Cancers
The therapeutic landscape of prostate cancer has expanded rapidly over the past 10 years, and there is now an even greater need to understand the biological mechanisms of resistance and to develop noninvasive biomarkers to guide treatment. The androgen receptor (AR) is known to be involved in the pathogenesis and progression of prostate cancer. Recently, highly sensitive next-generation sequencing and PCR-based methods for analyzing androgen receptor gene (AR) copy numbers (CN) and mutations in plasma were established in cell-free DNA (cfDNA) of patients with castration-resistant prostate cancer (CRPC) treated with different drugs. The study of cfDNA holds great promise for improving treatment in CRPC, especially in the advanced stage of the disease. Recent findings showed the significant association of plasma AR aberrations with clinical outcome in CRPC patients treated with AR-directed therapies, whereas no association was observed in patients treated with taxanes. This suggests t...
Egyptian Journal of Pathology, 2019
Background Prostate cancer (PCa) is one of the most commonly diagnosed male tumors all over the world. Most studies have concentrated upon the established role of epithelial androgen receptor (AR) expression in PCa, but the role of stromal AR expression is still not completely understood. Aim To assess immunohistochemical expression of stromal AR and investigate its relation to the PCa grade (according to the new contemporary advances in Gleason score/grading system) and other clinicopathological parameters. Materials and methods This is a retrospective study performed on 65 cases of PCa. All cases were immunohistochemically stained for AR to assess its stromal expression using the Allred score applied for estrogen receptor (ER) and progesterone receptor (PR) in the breast. The results were recorded for statistical analysis. Results Stromal AR was significantly related to the percentage of PCa in the specimen (P=0.003), tumor grade (P=0.001), perineural invasion (P=0.041), and cancer stage (P=0.001). On the contrary, stromal AR expression showed statistically insignificant relation with patients’ age (P=0.231), diabetes mellitus status (P=0.073), preoperative prostate-specific antigen level (P=0.202), digital rectal examination result (P=0.421), weight of the prostate (P=0.083), tumor size (P=0.209), and lymph node metastasis (P=0.411). Moreover, using Spearman’s correlation, there was a highly statistically significant correlation between stromal AR score and both Gleason grade/score (P<0.0001) and TNM/American Joint Committee on Cancer stage (P<0.0001). Conclusion AR expression in prostatic cancer stroma may have protective value against cancer progression.
PDF file - 3.8MB, Supplemental Figures. (S1) AR transcriptional signature derivation and validation. (S2) Time course for immunofluorescence assay for AR signaling. (S3) Time course for multiparameter single cell immunofluorescence assay for AR signaling applied to VCaP prostate cancer cells. (S4) Immunofluorescence images of LNCaP cells treated with R1881 or bicalutamide and captured on HB CTC-chip. (S5) Enumeration of CTCs in healthy donor controls, male patients without cancer, and metastatic prostate cancer patients. (S6) Kaplan-Meier survival curves for overall survival in patients treated with abiraterone acetate according to increase in % AR-on CTCs and PSA response.