PITX2 DNA Methylation as Biomarker for Individualized Risk Assessment of Prostate Cancer in Core Biopsies  Barbara Uhl, Heidrun Gevensleben, Yuri Tolkach, Verena Sailer, Michael Majores, Maria Jung, Sebastian Meller, Johannes Stein, Jörg Ellinger, Dimo Dietrich, Glen Kristiansen  The Journal of Molecular Diagnostics  Volume 19, Issue 1, Pages 107-114 (January 2017) DOI: 10.1016/j.jmoldx.2016.08.008 Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

Figure 1 PITX2 promoter methylation in matched tissue samples [prostate cancer (PCa), normal adjacent tissue (NAT), benign prostatic hyperplasia (BPH)] from 24 patients with PCa. PITX2 methylation reliably discriminates between tumor and normal or hyperplastic tissue. The gray line indicates median methylation. n = 22 (BPH); n = 24 (PCa and NAT). P < 0.001 (analysis of variance between groups PCa, NAT, and BPH; Kruskal-Wallis test). The Journal of Molecular Diagnostics 2017 19, 107-114DOI: (10.1016/j.jmoldx.2016.08.008) Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

Figure 2 Kaplan-Meier analysis of biochemical recurrence (BRC)–free survival in 260 patients with prostate cancer stratified by PITX2 methylation status. Patient classification into PITX2 low and PITX2 high groups was based on a previously well-established cut-off (6.43% methylation).23 Approximate mean BCR-free survival was 120 months (PITX2 low; 95% CI, 112–128 months) and 111 months (PITX2 high; 95% CI, 101–121 months), respectively. n = 138 (PITX2 low); n = 122 (PITX2 high). P = 0.043 (log-rank test). The Journal of Molecular Diagnostics 2017 19, 107-114DOI: (10.1016/j.jmoldx.2016.08.008) Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

Figure 3 PITX2 methylation in prostate biopsy samples from patients with prostate cancer (PCa) and benign prostatic disease (BPD). PITX2 methylation was significantly increased in tumor-positive biopsies of patients with PCa compared with tumor-negative cores of patients with PCa or BPD tissue (P < 0.001). Furthermore, there was a slight but significant difference between biopsy samples from patients with BPD and tumor-negative samples of patients with PCa. Light gray lines represent median methylation. n = 32 (PCa); n = 31 (BPD). P < 0.05(Kruskal-Wallis test). The Journal of Molecular Diagnostics 2017 19, 107-114DOI: (10.1016/j.jmoldx.2016.08.008) Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions