domingo, 30 de diciembre de 2012

Development and Clinical Validation of a Real-Ti... [J Mol Diagn. 2012] - PubMed - NCBI

Development and Clinical Validation of a Real-Ti... [J Mol Diagn. 2012] - PubMed - NCBI

J Mol Diagn. 2012 Dec 21. pii: S1525-1578(12)00306-6. doi: 10.1016/j.jmoldx.2012.11.002. [Epub ahead of print]

Development and Clinical Validation of a Real-Time PCR Assay for PITX2 DNA Methylation to Predict Prostate-Specific Antigen Recurrence in Prostate Cancer Patients Following Radical Prostatectomy.

Source

Institute of Pathology, University Hospital Bonn, Bonn, Germany. Electronic address: dimo.dietrich@gmail.com.

Abstract

Prostate cancer is the most common cancer among men. The prospective discrimination of aggressive and clinically insignificant tumors still poses a significant and, as yet, unsolved problem. PITX2 DNA methylation is a strong prognostic biomarker in prostate cancer. Recently, a diagnostic microarray for prostate cancer prognosis based on PITX2 methylation has been developed and validated. Because this microarray requires nonstandard laboratory equipment, its use in a diagnostic setting is limited. This study aimed to develop and validate an alternative quantitative real-time PCR assay for measuring PITX2 methylation that can easily be established in clinical laboratories, thereby facilitating the implementation of this biomarker in clinical practice. A methylation cut-off for patient stratification was established in a training cohort (n = 157) and validated in an independent test set (n = 523) of men treated with radical prostatectomy. In univariate Cox proportional hazards analysis, PITX2 hypermethylation was a significant predictor for biochemical recurrence (P < 0.001, hazard ratio = 2.614). Moreover, PITX2 hypermethylation added significant prognostic information (P = 0.003, hazard ratio = 1.814) to the Gleason score, pathological T stage, prostate-specific antigen, and surgical margins in a multivariate analysis. The clinical performance was particularly high in patients at intermediate risk (Gleason score of 7) and in samples containing high tumor cell content. This assay might aid in risk stratification and support the decision-making process when determining whether a patient might benefit from adjuvant treatment after radical prostatectomy.
Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.
PMID:
23266319
[PubMed - as supplied by publisher]

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