Τίτλος:
Persistent, biologically meaningful prostate cancer after 1 year of androgen ablation and docetaxel treatment
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Purpose: 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. Patients and 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. Conclusion: 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. © 2011 by American Society of Clinical Oncology.
Συγγραφείς:
Tzelepi, V.
Efstathiou, E.
Wen, S.
Troncoso, P.
Karlou, M.
Pettaway, C.A.
Pisters, L.L.
Hoang, A.
Logothetis, C.J.
Pagliaro, L.C.
Περιοδικό:
Journal of Clinical Oncology
Λέξεις-κλειδιά:
CD31 antigen; chromogranin; cytochrome P450 17; docetaxel; Ki 67 antigen; leuprorelin; molecular marker; protein bcl 2; protein p53; protein Patched; Smoothened protein; somatomedin C; sonic hedgehog protein; steroid 5alpha reductase 1; synaptophysin; transcription factor Gli1; transcription factor Gli2; vasculotropin, adult; advanced cancer; aged; androgen deprivation therapy; angiogenesis; article; cancer grading; cancer growth; cancer localization; cancer resistance; cancer surgery; clinical article; comparative study; controlled study; cystectomy; human; human cell; human tissue; immunohistochemistry; intracellular signaling; male; multiple cycle treatment; preoperative evaluation; priority journal; prostate cancer; prostatectomy; protein expression; tissue microarray, Adenocarcinoma; Adult; Aged; Androgens; Antineoplastic Agents, Phytogenic; Cell Adhesion Molecules; Combined Modality Therapy; Cystectomy; Disease Progression; Gene Expression Profiling; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Neoplastic Stem Cells; Neovascularization, Physiologic; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Signal Transduction; Taxoids; Time Factors; Tumor Markers, Biological
DOI:
10.1200/JCO.2010.33.2999
