title: PITX2 DNA Methylation as Biomarker for Individualized Risk Assessment of Prostate Cancer in Core Biopsies.
abstract: Hypermethylation of the paired-like homeodomain transcription factor 2 (PITX2) gene is a strong predictor of the risk of biochemical recurrence in patients with prostate cancer (PCa) after radical prostatectomy. We investigate whether PITX2 methylation is feasible for individualized risk assessment in prostate core biopsies before surgery. A quantitative, methylation-specific real-time PCR was used to measure PITX2 in three cohorts: i) matched samples of neoplastic and nonneoplastic tissue from 24 patients with PCa, ii) a well-characterized cohort of 300 patients with PCa after radical prostatectomy, and iii) core biopsy specimens from 32 patients with PCa and 31 patients with benign prostatic disease. PITX2 methylation discriminated between neoplastic and nonneoplastic tissue in patients with PCa (P < 0.001). In the second cohort, PITX2 methylation significantly correlated with clinicopathologic parameters, and PITX2 hypermethylation predicted an increased risk of biochemical recurrence in univariate Cox proportional hazards regression analysis (hazard ratio, 1.77; P = 0.046) and Kaplan-Meier analysis (P = 0.043). In 753 prostate biopsies, 720 (95.6%) were applicable for analysis, rendering the assay feasible for diagnostic biopsies. PITX2 methylation was furthermore significantly increased in tumor-positive biopsies and strongly correlated with International Society of Urological Pathology (ISUP) grade groups. This study indicates that the PITX2 methylation assay is feasible in prostate biopsies and might add valuable prognostic information for risk assessment in a presurgical diagnostic setting.
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Uhl
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Gevensleben
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Tolkach
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medicine of Cornell University, New York, New York; Englander Institute for Precision Medicine, Weill Cornell Medicine of Cornell University, New York, New York.
authors.forename: Verena
authors.initials: V
authors.lastname: Sailer
authors.affiliation: Institute of Dermatopathology, Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Majores
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Jung
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Meller
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Stein
authors.affiliation: Department of Urology, University Hospital Bonn, Bonn, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany; Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Bonn, Germany.
authors.forename: Dimo
authors.initials: D
authors.lastname: Dietrich
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany. Electronic address: glen.kristiansen@ukb.uni-bonn.de.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D062005:Biopsy, Large-Core Needle; D016022:Case-Control Studies; D019175:DNA Methylation; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D057285:Precision Medicine; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000473:pathology; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D018570:Risk Assessment; D014157:Transcription Factors / Q000235:genetics*; D000097577:Homeobox Protein PITX2
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2