Hyung Kyu Park1, So Dug Lim1, Ghee Young Kwon2. 1. Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea. 2. Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Abstract
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.
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.
Entities:
Keywords:
AR splice variants; AR-V7; Androgen receptor; castration-resistant prostate cancer
Authors: Elisabeth A Messner; Thomas M Steele; Maria Malvina Tsamouri; Nazila Hejazi; Allen C Gao; Maria Mudryj; Paramita M Ghosh Journal: Biomedicines Date: 2020-10-15
Authors: Zachery R Reichert; Tadas Kasputis; Srinivas Nallandhighal; Sophia M Abusamra; Amy Kasputis; Saloni Haruray; Yugang Wang; Shamara Williams; Udit Singhal; Ajjai Alva; Frank C Cackowski; Megan E V Caram; Phillip L Palmbos; Sarah E Yentz; David C Smith; Joshi J Alumkal; Todd M Morgan Journal: Int J Mol Sci Date: 2021-12-21 Impact factor: 6.208