© 2003 by Oxford University Press
© 2003 Oxford University Press
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Quantitative GSTP1 Methylation and the Detection of Prostate Adenocarcinoma in Sextant Biopsies
Affiliation of authors: Department of Otolaryngology-Head and Neck Surgery (SVH, DS), Department of Pathology (HES, JIE), Department of Urology (AAWP, PCW), Department of Biostatistics/Oncology (SNG), The Johns Hopkins University School of Medicine, Baltimore, MD.
Correspondence to: David Sidransky, MD, Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University School of Medicine, 818 Ross Research Bldg., 720 Rutland Ave., Baltimore, MD 21205-2196 (e-mail: dsidrans{at}jhmi.edu).
ABSTRACT
Hypermethylation of the 5' promoter region of the glutathione S-transferase
gene (GSTP1) occurs at a very high frequency in prostate adenocarcinoma. We compared the results of blinded histologic review of sextant biopsy samples from 72 excised prostates with those obtained using a quantitative methylation-specific polymerase chain reaction assay (QMSP) for GSTP1. Formal surgical pathologic review of the resected prostates was used to determine the number of patients with (n = 61) and without (n = 11) prostate cancer. Histology alone detected prostate carcinoma with 64% sensitivity (95% confidence interval [CI] = 51% to 76%) and 100% specificity (95% CI = 72% to 100%), whereas the combination of histology and GSTP1 QMSP at an assay threshold greater than 10 detected prostate carcinoma with 75% sensitivity (95% CI = 63% to 86%) and 100% specificity (95% CI = 72% to 100%), an 11% improvement (95% CI = 5% to 22%) in sensitivity over histology alone. The combination of histology and GSTP1 QMSP at an assay threshold greater than 5 detected prostate adenocarcinoma with 79% sensitivity (95% CI = 68% to 89%), a 15% improvement (95% CI = 7% to 26%) over histology alone. Thus, GSTP1 QMSP improved the sensitivity of histologic review of random needle biopsies for prostate cancer diagnosis. Further studies should determine whether detection of GSTP1 hypermethylation in a biopsy sample with normal histology indicates the need for an early repeat biopsy at the same site.
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