The role of steroid hormones in carcinogenesis of the prostate is to some extent unraveled thorough the effect of androgen deprivation therapy on prostate cancer (PCa) progression. Other members of the steroid hormone family, such as progesterone, are also implicated in PCa, but progesterone's role remains undefined. This study aimed to examine the distribution of progesterone receptor isoforms (PGRA, PGRB) in PCa tissue and their association with clinical endpoints. This was conducted retrospectively by collecting radical prostatectomy specimens from 535 patients. Tissue was analyzed using tissue microarray, where representative tumor areas were carefully selected. Protein expression was evaluated through immunohistochemistry, in stromal and epithelial tissue. Associations between receptor expression and clinical data were considered using statistical survival analyses. Herein, we discovered a solely stromal PGRA- and a stromal and epithelial PGRB expression. Further, a high PGRB expression in tumor tissue was associated with an unfavorable prognosis in both univariate and multivariate analyses: Biochemical failure (HR: 2.0, 95% CI: 1.45-2.76, p < 0.001) and clinical failure (HR: 2.5, 95% CI: 1.29-4.85, p = 0.006). These findings are in agreement with our previous investigation on pan-PGR, indicating that the observed negative effect of PGR is represented by PGRB.
Scientific reports. 2018 Jul 27*** epublish ***
Thea Grindstad, Elin Richardsen, Sigve Andersen, Kaja Skjefstad, Mehrdad Rakaee Khanehkenari, Tom Donnem, Nora Ness, Yngve Nordby, Roy M Bremnes, Samer Al-Saad, Lill-Tove Busund
Department of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway. ., Department of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway., Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.