Distinct DNA methylation alterations are associated with cribriform architecture and intraductal carcinoma in Gleason pattern 4 prostate tumors

Olkhov‑Mitsel,Ekaterina; Siadat,Farshid; Kron,Ken; Liu,Liyang; Savio,Andrea  J.; Trachtenberg,John; Fleshner,Neil; van der Kwast,Theodorus; Bapat,Bharati

doi:10.3892/ol.2017.6140

Distinct DNA methylation alterations are associated with cribriform architecture and intraductal carcinoma in Gleason pattern 4 prostate tumors

Authors:
- Ekaterina Olkhov‑Mitsel
- Farshid Siadat
- Ken Kron
- Liyang Liu
- Andrea J. Savio
- John Trachtenberg
- Neil Fleshner
- Theodorus van der Kwast
- Bharati Bapat
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Affiliations: Lunenfeld‑Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5T3L9, Canada, Department of Anatomical Pathology, Royal Alexandra Hospital, Edmonton, AB T5H3V9, Canada, Ontario Cancer Institute, Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G0A3, Canada, Division of Urology, Department of Surgical Oncology, University Health Network, University of Toronto, Toronto, ON M5G2M9, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S1A1, Canada
Published online on: May 9, 2017 https://doi.org/10.3892/ol.2017.6140
Pages: 390-396

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Abstract

The aim of the present study was to explore DNA methylation aberrations in association with cribriform architecture and intraductal carcinoma (IDC) of the prostate, as there is robust evidence that these morphological features are associated with aggressive disease and have significant clinical implications. Herein, the associations of a panel of seven known prognostic DNA methylation biomarkers with cribriform and IDC features were examined in a series of 91 Gleason pattern (GP) 4 tumors derived from Gleason score 7 radical prostatectomies. Gene specific DNA methylation was compared between cribriform and/or IDC positive vs. negative cases, and in association with clinicopathological features, using Chi square and Mann‑Whitney U tests. DNA methylation of the adenomatous polyposis coli, Ras association domain family member 1 and T‑box 15 genes was significantly elevated in GP4 tumors with cribriform and/or IDC features compared with negative cases (P=0.045, P=0.007 and P=0.013, respectively). To the best of our knowledge, this provides the first evidence for an association between cribriform and/or IDC and methylation biomarkers, and warrants further investigation of additional DNA methylation events in association with various architectural patterns in prostate cancer.

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