PITX2 Promoter Methylation Status Is an Independent Prognostic Marker for Biochemical Recurrence in Patients with Prostate Cancer after Radical Prostatectomy
E Castanos-Velez, C Bangma, S Freedland, A Hartmann, M Ittmann, P Schatz, L Sun, A van Leenders, G Weiss, TM Wheeler. Epigenomics AG, Berlin, Germany; Erasmus MC, Rotterdam, Netherlands; Durham VA Medical Center, Durham, NC; University of Erlangen, Erlangen, Germany; Baylor College of Medicine, Houston, TX; Duke University Medical Center, Durham, NC
Background: We have developed a test that measures the methylation status of the PITX2 gene promoter qualitatively, that correlates with the probability of biochemical recurrence of prostate cancer after radical prostatectomy. The assay uses FFPE tumor tissue samples and the Affymetrix Genechip system, with a customized microarray (Epichip PITX2).
Design: Here we present the results of a clinical investigation including almost 500 patients from four different cohorts in the USA and Europe.
Results: We demonstrated a significantly higher risk for biochemical recurrence in patients with a high methylation status result, when compared to patients with low methylation status (HR = 3.0, 95% CI: 2.0 4.5, p < 10-5). The probability of being free of biochemical recurrence at 5 years after surgery was 85% for patients in the low methylation group and only 61% for patients in the high methylation group. In the group of patients with Gleason score 7 the relative risk of suffering from a biochemical recurrence is twice as large for a patient from the high methylation group when compared to the low methylation patient group (HR = 2.0, 95% CI: 1.2 3.3, p = 0.005). The probability of being free of biochemical recurrence at 5 years after surgery was 79% for patients in the low methylation group and only 62% for patients in the high methylation group.
Conclusions: The PCMCT assay defines a group of patients most likely to experience biochemical recurrence. This test adds to the information currently provided by clinical and histological analysis to stratify the patient population, and especially patients diagnosed with Gleason score 7 could benefit from this new tool for biochemical relapse risk stratification.
Category: Genitourinary (including renal tumors)
Tuesday, March 10, 2009 9:00 AM
Platform Session: Section A, Tuesday Morning