title: Increased expression of putative cancer stem cell markers in primary prostate cancer is associated with progression of bone metastases.
abstract: BACKGROUND
  A number of putative stem cell markers have been associated with aggressiveness of prostate cancer, including alpha 2 and alpha 6 integrin and c-met. The study aimed to test the hypothesis that the development of bone metastasis correlates with the proportion of prostate cancer stem cell-like cells present in the primary tumor.
  
  
  METHODS
  Prostate tissue samples were obtained from patients with high-risk prostatic adenocarcinoma. Prostate cancer tumor tissue samples underwent immunohistochemical staining for alpha 2 and alpha 6 integrin and c-met; positive and negative controls were included. Samples were scored as positive if >5% of cells within the sample stained positively. Survival and bone metastasis-free survival curves on the patient cohort were estimated by the actuarial method of Kaplan-Meier.
  
  
  RESULTS
  A total of 62 patients were included in the study. Bone metastases progression rate was 46% at 105 months with a median time of 46 months (95% CI: 1-62.5 months); prostate cancer-specific survival was 33% at 122 months with a median survival time of 69.4 months (95% CI: 63.5-109.4 months). Survival curves show that c-met-, alpha 2, and alpha 6 integrin-positive tumors were positively associated with the occurrence of bone metastasis-free survival. There was a higher level of significance when at least c-met and either alpha 2 or alpha 6 integrin was positive.
  
  
  CONCLUSIONS
  It can be concluded that percentage of stem cell-like prostate cancer cells has a prognostic impact especially on the risk of metastatic bone progression.
authors: Service d'Urologie et Chirurgie de la Transplantation, Université Lyon 1, Lyon, France. marc.colombel@chu-lyon.fr
authors: Marc
authors: M
authors: Colombel
authors: Colby L
authors: CL
authors: Eaton
authors: Freddy
authors: F
authors: Hamdy
authors: Estelle
authors: E
authors: Ricci
authors: Gabri
authors: G
authors: van der Pluijm
authors: Marco
authors: M
authors: Cecchini
authors: Florence
authors: F
authors: Mege-Lechevallier
authors: Philippe
authors: P
authors: Clezardin
authors: George
authors: G
authors: Thalmann
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary* / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary*; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D039421:Integrin alpha2 / Q000032:analysis; D039503:Integrin alpha6 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D039421:Integrin alpha2; D039503:Integrin alpha6; D019859:Proto-Oncogene Proteins c-met