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Korean J Urol Oncol > Volume 10(1); 2012 > Article
The Korean Journal of Urological Oncology 2012;10(1): 21-26.
전립선암의 호르몬 불응성과 PTEN, CD44 발현양상의 연관성 분석
함원식, 박재원, 조강수, 이창기, 최영득, 홍성준
연세대학교 의과대학 비뇨기과학교실, 비뇨의과학연구소
The Analysis of Relationship between Refractoriness to Androgen Deprivation and PTEN, CD44 Expression in Prostate Cancer
Won Sik Ham , Jae Won Park , Kang Su Cho , Chang Kee Lee , Young Deuk Choi , Sung Joon Hong
Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea
Published online: April 30, 2012.
ABSTRACT
Purpose:
Most prostate cancers (PCs) ultimately progress to castration resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT). Because cancer stem cells survive ADT, which can lead to tumor recurrence and understanding the molecular changes that occur after ADT would helpful for finding novel therapies targeting CRPC, we analyzed the expression of CD44, a stem cell marker in radical prostatectomy samples after ADT.
Materials and Methods:
PTEN and CD44 expression profiles were determined by microarray or real-time PCR in 107 radical prostatectomy specimens from patients given neoadjuvant ADT. Pathological regressive changes and the correlation of postoperative biochemical failure with PTEN and CD44 expression were analyzed.
Results:
As the PC tissues had minimal regression effects after ADT, they showed significantly advanced pathological stage (p=0.001), PTEN inactivation (p<0.001), and high CD44 expression (p<0.001). The PTEN inactivation group showed a significantly higher probability of positive CD44 expression compared to the non-PTEN inactivation group (OR 10.5, 95% CI 4.0 to 27.6, p<0.001). Cox regression analysis revealed that seminal vesicle invasion, biopsy Gleason score, and CD44 expression were significantly associated with the time to biochemical recurrence.
Conclusions:
PC tissues refractory to ADT showed PTEN inactivation with high CD44 expression. The PTEN inactivation group showed a significantly high probability of positive CD44 expression. Our results support that the PTEN/PI3K/Akt pathways are necessary for prostate cancer stem cell maintenance. (Korean J Urol Oncol 2012;10:21-26)
Key Words: Prostate neoplasms; PTEN; PI3K/Akt; CD44
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