Sunday June 30, 2019 from 07:30 to 09:00
Validation of the prognostic value of NF-κB p65 in prostate cancer using a large multi-institutional cohort of the Canadian Prostate Cancer Biomarker Network
Andrée-Anne Grosset1, Veronique Ouellet1, Christine Caron1, Gabriela Fragoso1, Veronique Barres1, Nathalie Delvoye1, Mathieu Latour1, Armen G. Aprikian2, Alain Bergeron3, Simone Chevalier2, Ladan Fazli4, Neil E. Fleshner5, Martin E. Gleave4, Pierre Karakiewicz1, Louis Lacombe3, Jean-Baptiste Lattouf1, Theodorus van der Kwast5, Dominique Trudel1, Anne-Marie Mes-Masson1, Fred Saad1.
1Axe Cancer/Institut du Cancer de Montréal, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada; 2Surgery and Urology, Research Institute - McGill University Health Centre, Montréal, QC, Canada; 3Axe Oncologie, Centre Hospitalier Universitaire de Québec et Universtié Laval, Québec City, QC, Canada; 4Vancouver Prostate Centre, Vancouver, BC, Canada; 5University Health Network, Toronto, ON, Canada
Canadian Prostate Cancer Biomarker Network (CPCBN). Terry Fox Research Institute.
Introduction: The identification of patients with high-risk prostate cancer (PCa) is a major challenge for clinicians, and the improvement of current prognostic parameters is an unmet clinical need. We and others have identified the association between the nuclear localization of NF-κB p65 (p65) and biochemical recurrence (BCR) in PCa in small and/or single-centre cohorts of patients.
Methods: In this study, we accessed two different multicentre tissue microarrays (TMAs) representing cohorts of patients (Test-TMA and Validation-TMA series) of the Canadian Prostate Cancer Biomarker Network (CPCBN) to validate the association between nuclear p65 expression and PCa outcomes. Immunohistochemical staining of p65 was performed on the Test-TMA and the Validation-TMA series, which include PCa tissues from patients treated by first-line radical prostatectomy (n=250 and n=1262, respectively). Two independent observers evaluated the frequency of nuclear p65 expression on digital images in either benign adjacent glands or cancer cells. Kaplan-Meier curves coupled with a log-rank test and univariate and multivariate Cox regression models were used for statistical analyses of continuous values and dichotomized data (cutoff of 3%) of nuclear p65.
Results: Kaplan-Meier analyses showed that patients with a higher frequency of nuclear p65 had an increased risk of progression (biochemical relapse and bone metastasis development) and mortality (p<0.05). When combined with preoperative prostate-specific antigen (PSA), Gleason grade, margin status, and pTNM, nuclear p65 expression remained significant in Cox regression analyses. Indeed, patients with higher level of nuclear p65 presented an increase risk progression using three different endpoints: biochemical relapse (hazard ratio [HR] 1.33; p=0.005), development of bone metastases (HR 1.82; p=0.033), and PCa-specific mortality (HR 2.63; p=0.033).
Conclusions: We report the first study using the pan-Canadian multicentre cohorts of CPCBN and validate the association between increased frequency of nuclear p65 expression and risk of disease progression.
 Ouellet V, Aprikian A, Bergeron A, et al. The Terry Fox Research Institute Canadian Prostate Cancer Biomarker Network: A descriptive analysis of a pan-Canadian, multicentre cohort for biomarker validation. BMC Urol 2018;18:78. https://doi.org/10.1186/s12894-018-0392-x