Identification of a unique epigenetic sub-microenvironment in prostate cancer

J. Rodriguez-Canales, J. C. Hanson, M. A. Tangrea, H. S. Erickson, P. S. Albert, B. S. Wallis, A. M. Richardson, P. A. Pinto, W. M. Linehan, J. W. Gillespie, M. J. Merino, S. K. Libutti, K. G. Woodson, M. R. Emmert-Buck, R. F. Chuaqui

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

The glutathione S-transferase P1 (GSTP1) gene promoter is methylated in tumour cells in more than 90% of prostate carcinomas. Recently, GSTP1 promoter methylation was identified in tumour-associated stromal cells in addition to the tumour epithelium. To define the extent and location of stromal methylation, epigenetic mapping using pyrosequencing quantification of GSTP1 promoter methylation and an anatomical three-dimensional reconstruction of an entire human prostate specimen with cancer were performed. Normal epithelium and stroma, tumour epithelium, and tumour-associated stromal cells were laser capture-microdissected from multiple locations throughout the gland. As expected, the GSTP1 promoter in both normal epithelium and normal stromal cells distant from the tumour was not methylated and the tumour epithelium showed consistently high levels of promoter methylation throughout However, tumour-associated stromal cells were found to be methylated only in a localized and distinct anatomical sub-field of the tumour, revealing the presence of an epigenetically unique microenvironment within the cancer. Morphologically, the sub-field consisted of typical, non-reactive stroma, representing a genomic alteration in cells that appeared otherwise histologically normal. Similar epigenetic anatomical mapping of a control prostate gland without cancer showed low background methylation levels in all cell types throughout the specimen. These data suggest that stromal cell methylation can occur in a distinct sub-region of prostate cancer and may have implications for understanding tumour biology and clinical intervention.

Original languageEnglish (US)
Pages (from-to)410-419
Number of pages10
JournalJournal of Pathology
Volume211
Issue number4
DOIs
StatePublished - Mar 1 2007

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Keywords

  • GSTP1
  • Methylation
  • Prostate carcinoma
  • Tumour microenvironment
  • Tumour stroma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Rodriguez-Canales, J., Hanson, J. C., Tangrea, M. A., Erickson, H. S., Albert, P. S., Wallis, B. S., Richardson, A. M., Pinto, P. A., Linehan, W. M., Gillespie, J. W., Merino, M. J., Libutti, S. K., Woodson, K. G., Emmert-Buck, M. R., & Chuaqui, R. F. (2007). Identification of a unique epigenetic sub-microenvironment in prostate cancer. Journal of Pathology, 211(4), 410-419. https://doi.org/10.1002/path.2133