mRNA expressions of androgen receptor and its variants in matched hormone-sensitive and castration-resistant prostate cancer

Objectives: Androgen receptor splice variants (AR-Vs), especially androgen receptor splice variant 7 (AR-V7), are considered as important factors in developing castration-resistance of prostate cancer and also as candidate predictive factors. Our aim was to evaluate changes in the mRNA expression of full-length AR (AR-FL) and AR-Vs in the primary prostate cancers from the same patients before and after ADT. Methods: We compared morphologic differences and evaluated AR-FL, AR-V7, AR-V4, ARv567es, AR-V3 and AR8 mRNA expression in matched samples of primary hormone-sensitive and castration-resistant prostate cancer (CRPC) from 19 patients. Results: mRNA expression of AR-FL, AR-V7, ARv567es and AR-V3 was present in hormone sensitive prostate cancer (HSPC) and was significantly increased in CRPC in 81.2% (13/16). There were strong positive correlations between AR-FL and AR-V7 (r = 0.93, p <.001), ARv567es (r = 0.72, p <.001) and AR-V3 (r = 0.81, p <.001) mRNA expression. AR-V7/AR-FL ratio was more significantly (>30%) increased after ADT in 25% (4/16) of the patients, who showed significantly (p <.001) worse overall survival. Neuroendocrine differentiation was seen in one patient (5.3%) and the Gleason score was increased in 10 (52.6%) patients. Conclusion: We demonstrated that the expression of AR-V7 is present at low levels in HSPC and is increased in CRPC and the increase is an active process possibly related to aggressive clinical course.