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KMID : 1001020120100010021
Korean Journal of Urological Oncology
2012 Volume.10 No. 1 p.21 ~ p.26
The Analysis of Relationship between Refractoriness to Androgen Deprivation and PTEN, CD44 Expression in Prostate Cancer
Ham Won-Sik

Park Jae-Won
Cho Kang-Su
Lee Chang-Kee
Choi Young-Deuk
Hong Sung-Joon
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£¼0.001), and high CD44 expression (p£¼0.001). 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£¼0.001). 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.
KEYWORD
Prostate neoplasms, PTEN, PI3K/Akt, CD44
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