title: Persistent, biologically meaningful prostate cancer after 1 year of androgen ablation and docetaxel treatment.
abstract: OBJECTIVE
  Clinicians are increasingly willing to treat prostate cancer within the primary site in the presence of regional lymph node or even limited distant metastases. However, no formal study on the merits of this approach has been reported. We used a preoperative clinical discovery platform to prioritize pathways for assessment as therapeutic targets and to test the hypothesis that the primary site harbors potentially lethal tumors after aggressive treatment.
  
  
  METHODS
  Patients with locally advanced or lymph node-metastatic prostate cancer underwent 1 year of androgen ablation and three cycles of docetaxel therapy, followed by prostatectomy. All specimens were characterized for stage by accepted criteria. Expression of select molecular markers implicated in disease progression and therapy resistance was determined immunohistochemically and compared with that in 30 archived specimens from untreated patients with high-grade prostate cancer. Marker expression was divided into three groups: intracellular signaling pathways, stromal-epithelial interaction pathways, and angiogenesis.
  
  
  RESULTS
  Forty patients were enrolled, 30 (75%) of whom underwent prostatectomy and two (5%) who underwent cystoprostatectomy. Twenty-nine specimens contained sufficient residual tumor for inclusion in a tissue microarray. Immunohistochemical analysis showed increased epithelial and stromal expression of CYP17, SRD5A1, and Hedgehog pathway components, and modulations of the insulin-like growth factor I pathway.
  
  
  CONCLUSIONS
  A network of molecular pathways reportedly linked to prostate cancer progression is activated after 1 year of therapy; biomarker expression suggests that potentially lethal cancers persist in the primary tumor and may contribute to progression.
authors: The University of Texas MD Anderson Cancer Center, 1155 Pressler St, Houston, TX 77030-3721, USA.
authors: Vassiliki
authors: V
authors: Tzelepi
authors: Eleni
authors: E
authors: Efstathiou
authors: Sijin
authors: S
authors: Wen
authors: Patricia
authors: P
authors: Troncoso
authors: Maria
authors: M
authors: Karlou
authors: Curtis A
authors: CA
authors: Pettaway
authors: Louis L
authors: LL
authors: Pisters
authors: Anh
authors: A
authors: Hoang
authors: Christopher J
authors: CJ
authors: Logothetis
authors: Lance C
authors: LC
authors: Pagliaro
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