| Autor: |
Dietrich, Dimo, Hasinger, Oliver, Bañez, Lionel L., Sun, Leon, van Leenders, Geert J., Wheeler, Thomas M., Bangma, Chris H., Wernert, Nicolas, Perner, Sven, Freedland, Stephen J., Corman, John M., Ittmann, Michael M., Lark, Amy L., Madden, John F., Hartmann, Arndt, Schatz, Philipp, Kristiansen, Glen |
| Zdroj: |
The Journal of Molecular Diagnostics; March 2013, Vol. 15 Issue: 2 p270-279, 10p |
| Abstrakt: |
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. PITX2DNA methylation is a strong prognostic biomarker in prostate cancer. Recently, a diagnostic microarray for prostate cancer prognosis based on PITX2methylation 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 PITX2methylation 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, PITX2hypermethylation was a significant predictor for biochemical recurrence (P< 0.001, hazard ratio = 2.614). Moreover, PITX2hypermethylation 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. |
| Databáze: |
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