Increased expression of putative cancer stem cell markers in primary prostate cancer is associated with progression of bone metastases

Prostate. 2012 May 15;72(7):713-20. doi: 10.1002/pros.21473. Epub 2011 Aug 31.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / secondary*
  • Adenocarcinoma / surgery
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / secondary*
  • Cohort Studies
  • Disease Progression
  • Disease-Free Survival
  • Humans
  • Integrin alpha2 / analysis
  • Integrin alpha6 / analysis
  • Male
  • Middle Aged
  • Neoplastic Stem Cells / metabolism*
  • Prognosis
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / surgery
  • Proto-Oncogene Proteins c-met / analysis

Substances

  • Biomarkers, Tumor
  • Integrin alpha2
  • Integrin alpha6
  • Proto-Oncogene Proteins c-met