Neil Fleshner

MD, MPH, FRCSC

Phone

(416) 946-4501 ext. 2899

Assistant(s)

Biography

Dr. Neil Fleshner is Chair and Professor at the Division of Urology, University of Toronto. Dr. Fleshner is certified in both urology and epidemiology. He earned his MPH degree from the School of Public Health at Columbia University and completed his oncology training at Memorial Sloan Kettering Cancer Center.

Dr. Fleshner is an avid music lover and father of three.

Areas of Specialty and Research Interests

Aside from surgical practice, Dr. Fleshner conducts research on urologic cancer prevention with an emphasis on prostate cancer. He has authored over 400 scientific papers. Dr. Fleshner's current research projects include 2 randomized trials of nutritional intervention in prostate cancer as well as laboratory work assessing oxidative biomarkers and cell cycle regulation in prostate cancer cells exposed to micronutrients.

Affiliated Hospital(s)

Mount Sinai Hospital, Princess Margaret Cancer Centre (UHN), Toronto General Hospital (UHN)
 
 

Latest Publications

GBX2 Methylation Is a Novel Prognostic Biomarker and Improves Prediction of Biochemical Recurrence Among Patients with Prostate Cancer Negative for Intraductal Carcinoma and Cribriform Architecture.

Related Articles

GBX2 Methylation Is a Novel Prognostic Biomarker and Improves Prediction of Biochemical Recurrence Among Patients with Prostate Cancer Negative for Intraductal Carcinoma and Cribriform Architecture.

Eur Urol Oncol. 2019 May;2(3):231-238

Authors: Jeyapala R, Savio AJ, Olkhov-Mitsel E, Kamdar S, Zhao F, Cuizon C, Liu RSC, Zlotta A, Fleshner N, van der Kwast T, Bapat B

Abstract
BACKGROUND: Tumor intraductal carcinoma/cribriform architecture (IDC/C) is associated with an unfavorable prognosis and biochemical recurrence (BCR) in prostate cancer (PCa). Up to 70% of PCa patients are IDC/C-negative, but it is estimated that 20% of these cases still experience BCR. Thus, biomarkers for better detection of aggressive disease in IDC/C-negative patients are required.
OBJECTIVE: To investigate tumor-specific methylation of the transcription factor GBX2 as a novel prognosticator and predictor of BCR in PCa patients stratified by histopathologic features including IDC/C.
DESIGN, SETTING, AND PARTICIPANTS: Using genome-wide methylome profiling, we identified higher GBX2 methylation in grade group (GG) 4 tumors compared to GG1 (discovery cohort). The prognostic nature of GBX2 methylation was validated in silico using The Cancer Genome Atlas data (n=478) and a quantitative methylation assay for radical prostatectomy samples (n=254). Regulation of GBX2 methylation was investigated in prostate cells using methyl-CpG-binding domain sequencing and methylation analysis in functional knockouts of TET2, a key epigenetic player in prostate carcinogenesis.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The association of GBX2 methylation with Gleason score (GS), pathologic stage (pT), IDC/C, and BCR was analyzed using Kruskal-Wallis and Mann-Whitney tests. Univariate and multivariate Cox regression analyses were used to predict BCR.
RESULTS: GBX2 methylation was associated with GS (p<0.05), pT (p<0.01), and BCR (p<0.05). GBX2 methylation (p=0.004), GS (p<0.001), pT (p=0.012), and prostate-specific antigen (p=0.005) were independent predictors of BCR. Among IDC/C-negative patients, GBX2 methylation improved prediction of BCR (p=0.002). Loss of TET2 in prostate cells resulted in greater GBX2 methylation.
CONCLUSIONS: We identified GBX2 methylation as a novel prognostic factor in PCa and an independent predictor of BCR. We demonstrated the additive value of GBX2 methylation in predicting BCR among IDC/C-negative patients and elucidated a novel TET2-mediated upstream epigenetic regulatory mechanism of GBX2.
PATIENT SUMMARY: We identified GBX2 methylation as a promising prognostic biomarker that could improve the identification of prostate cancer patients at higher risk of biochemical recurrence.

PMID: 31200836 [PubMed - in process]