Molecular detection of prostate cancer in urine by GSTP1 hypermethylation

P. Cairns, M. Esteller, J. G. Herman, M. Schoenberg, Mark P. Schoenberg, M. Sanchez-Cespedes, N. H. Chow, M. Grasso, L. Wu, W. B. Westra, D. Sidransky

Research output: Contribution to journalArticle

257 Citations (Scopus)

Abstract

Novel approaches for the early detection and management of prostate cancer are urgently needed. Clonal genetic alterations have been used as targets for the detection of neoplastic cells in bodily fluids from many cancer types. A similar strategy for molecular diagnosis of prostate cancer requires a common and/or early genetic alteration as a specific target for neoplastic prostate cells. Hypermethylation of regulatory sequences at the glutathione S-transferase pi (GSTP1) gene locus is found in the majority (>90%) of primary prostate carcinomas, but not in normal prostatic tissue or other normal tissues. We hypothesized that urine from prostate cancer patients might contain shed neoplastic cells or debris amenable to DNA analysis. Matched specimens of primary tumor, peripheral blood lymphocytes (normal control), and simple voided urine were collected from 28 patients with prostate cancer of a clinical stage amenable to cure. Genomic DNA was isolated from the samples, and the methylation status of GSTP1 was examined in a blinded manner using methylation-specific PCR. Decoding of the results revealed that 22 of 28 (79%) prostate tumors were positive for GSTP1 methylation. In 6 of 22 (27%) cases, the corresponding urine-sediment DNA was positive for GSTP1 methylation, indicating the presence of neoplastic DNA in the urine. Furthermore, there was no case where urine-sediment DNA harbored methylation when the corresponding tumor was negative. Although we only detected GSTP1 methylation in under one-third of voided urine samples, we have demonstrated that molecular diagnosis of prostate neoplasia in urine is feasible. Larger studies focusing on carcinoma size, location in the prostate, and urine collection techniques, as well as more sensitive technology, may lead to the useful application of GSTP1 hypermethylation in prostate cancer diagnosis and management.

Original languageEnglish (US)
Pages (from-to)2727-2730
Number of pages4
JournalClinical Cancer Research
Volume7
Issue number9
StatePublished - 2001
Externally publishedYes

Fingerprint

Prostatic Neoplasms
Urine
Methylation
Prostate
DNA
Neoplasms
Glutathione S-Transferase pi
Carcinoma
Urine Specimen Collection
DNA Methylation
Lymphocytes
Technology
Polymerase Chain Reaction
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cairns, P., Esteller, M., Herman, J. G., Schoenberg, M., Schoenberg, M. P., Sanchez-Cespedes, M., ... Sidransky, D. (2001). Molecular detection of prostate cancer in urine by GSTP1 hypermethylation. Clinical Cancer Research, 7(9), 2727-2730.

Molecular detection of prostate cancer in urine by GSTP1 hypermethylation. / Cairns, P.; Esteller, M.; Herman, J. G.; Schoenberg, M.; Schoenberg, Mark P.; Sanchez-Cespedes, M.; Chow, N. H.; Grasso, M.; Wu, L.; Westra, W. B.; Sidransky, D.

In: Clinical Cancer Research, Vol. 7, No. 9, 2001, p. 2727-2730.

Research output: Contribution to journalArticle

Cairns, P, Esteller, M, Herman, JG, Schoenberg, M, Schoenberg, MP, Sanchez-Cespedes, M, Chow, NH, Grasso, M, Wu, L, Westra, WB & Sidransky, D 2001, 'Molecular detection of prostate cancer in urine by GSTP1 hypermethylation', Clinical Cancer Research, vol. 7, no. 9, pp. 2727-2730.
Cairns P, Esteller M, Herman JG, Schoenberg M, Schoenberg MP, Sanchez-Cespedes M et al. Molecular detection of prostate cancer in urine by GSTP1 hypermethylation. Clinical Cancer Research. 2001;7(9):2727-2730.
Cairns, P. ; Esteller, M. ; Herman, J. G. ; Schoenberg, M. ; Schoenberg, Mark P. ; Sanchez-Cespedes, M. ; Chow, N. H. ; Grasso, M. ; Wu, L. ; Westra, W. B. ; Sidransky, D. / Molecular detection of prostate cancer in urine by GSTP1 hypermethylation. In: Clinical Cancer Research. 2001 ; Vol. 7, No. 9. pp. 2727-2730.
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