Methylation markers in prostate biopsies are prognosticators for late biochemical recurrence and therapy after surgery in prostate cancer patients.

After diagnosis of prostate cancer is confirmed by a positive biopsy, the tumor may be surgically removed via radical prostatectomy (RP). However, many prostate cancer patients experience biochemical recurrence post-surgery and/or undergo salvage radiotherapy or hormone therapy. Timely treatment is required to prevent the spread of disease in these cases, and biopsy tissue may hold potential for disease prognostication before surgery is ever performed. We previously developed a prognostic multi-gene methylation panel in RP specimens, including APC, CRIP3, HOXD3, and TGFB2. In the current study, this panel was applied to a cohort of biopsy specimens (n=86), which were assessed for DNA methylation using the qPCR-based multiplex MethyLight. The biopsy-based methylation panel is significantly associated with biochemical recurrence when combined with the current clinical parameter of prostate-specific antigen (PSA) levels at diagnosis, and is able to prognosticate the initiation of salvage radiotherapy, where it outperforms PSA, and/or hormone therapy following RP. Additionally, this methylation panel is significantly associated with late recurrence occurring within five and seven years after surgery, when combined with PSA at diagnosis. Combining DNA methylation and clinicopathologic markers at the biopsy stage will not only increase their prognostic ability, but will also ensure effective patient management.

The Journal of molecular diagnostics : JMD. 2019 Oct 09 [Epub ahead of print]

Andrea J Savio, Shivani Kamdar, Renu Jeyapala, Ekaterina Olkhov-Mitsel, Carmelle Cuizon, Antonio Finelli, Alexandre R Zlotta, Ants Toi, Neil E Fleshner, Theodorus van der Kwast, Bharati Bapat

Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto., Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto; Department of Laboratory Medicine & Pathobiology., Department of Laboratory Medicine & Pathobiology; Institute of Medical Science., Division of Urology., Department of Surgery,; Department of Surgical Oncology, Urology Division, University Health Network, Toronto., Mount Sinai Hospital, Sinai Health System, Toronto., Department of Surgical Oncology, Division of Urology., Department of Pathology, Laboratory Medicine Program., Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto; Department of Laboratory Medicine & Pathobiology; Division of Urology,. Electronic address: .