Andrea Bakker1, Jonathan C Slack1, Nalla Palanisamy2, Shannon Carskadon2, Sunita Ghosh3,4, Ibrahim Khalifeh5, Tarek A Bismar6,7,8. 1. Department of Pathology and Laboratory Medicine, Alberta Precision Laboratories, University of Calgary Cumming School of Medicine, Rockyview General Hospital, Calgary, AB, T2V 1P9, Canada. 2. Department of Urology, Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, USA. 3. Department of Medical Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. 4. Departments of Mathematical and Statistical Sciences, University of Alberta, Edmonton, AB, Canada. 5. Department of Pathology and Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon. 6. Department of Pathology and Laboratory Medicine, Alberta Precision Laboratories, University of Calgary Cumming School of Medicine, Rockyview General Hospital, Calgary, AB, T2V 1P9, Canada. tabismar@ucalgary.ca. 7. Departments of Oncology, Biochemistry, and Molecular Biology, Calgary, AB, Canada. tabismar@ucalgary.ca. 8. Arnie Charbonneau Cancer Institute and Tom Baker Cancer Center, Calgary, AB, Canada. tabismar@ucalgary.ca.
Abstract
BACKGROUND: KLK4::KLKP1 fusion is a recently described pseudogene that is enriched in prostate cancer (PCa). This new biomarker has not been characterized in the Middle Eastern population. OBJECTIVE: To establish the incidence and prognostic value of KLK4::KLKP1 fusion in a cohort of Middle Eastern men with PCa and explore the relationship of this marker to other relevant biomarkers (PTEN, ERG, SPINK1). DESIGN, SETTING, AND PARTICIPANTS: We interrogated a cohort of 340 Middle Eastern men with localized PCa treated by radical prostatectomy between 2005 and 2015. KLK4::KLKP1 fusion status was assessed by RNA Chromogenic in situ hybridization (CISH) and correlated to pathological and clinical parameters. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: RNA-CISH expression of KLK4::KLKP1 was correlated with prognostic factors, ERG, PTEN, and SPINK1 expression, and biochemical recurrence (BCR) following prostatectomy. RESULTS AND LIMITATIONS: 51.7% of patient samples showed positive KLK4::KLKP1 expression; more commonly in cores of PCa (38%) versus non-cancer (20.6%) (p < 0.0001) and in lower Gleason Grade Group tumors (1-3) vs (4-5). KLK4::KLKP1 expression positively correlated with ERG positivity and inversely associated with PTEN loss. No significant association was found with SPINK1 expression, seminal vesicle invasion, positive surgical margin, pathological stage, or patient age (< 50 or ≥ 50). The association between PTEN loss and BCR increased when combined with KLK4::KLKP1 negativity (HR 2.31, CI 1.03-5.20, p = 0.042). CONCLUSIONS: KLK4::KLKP1 expression is more common in this cohort of Middle Eastern men than has been reported in North American men. It is associated with ERG positivity and inversely correlated with PTEN loss. In isolation, KLK4::KLKP1 expression was not significantly associated with clinical outcome or pathological parameters. However, its expression is associated with certain molecular subtypes (ERG-positive, PTEN-intact) and as we demonstrate may help further stratify the risk of recurrence within these groups.
BACKGROUND: KLK4::KLKP1 fusion is a recently described pseudogene that is enriched in prostate cancer (PCa). This new biomarker has not been characterized in the Middle Eastern population. OBJECTIVE: To establish the incidence and prognostic value of KLK4::KLKP1 fusion in a cohort of Middle Eastern men with PCa and explore the relationship of this marker to other relevant biomarkers (PTEN, ERG, SPINK1). DESIGN, SETTING, AND PARTICIPANTS: We interrogated a cohort of 340 Middle Eastern men with localized PCa treated by radical prostatectomy between 2005 and 2015. KLK4::KLKP1 fusion status was assessed by RNA Chromogenic in situ hybridization (CISH) and correlated to pathological and clinical parameters. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: RNA-CISH expression of KLK4::KLKP1 was correlated with prognostic factors, ERG, PTEN, and SPINK1 expression, and biochemical recurrence (BCR) following prostatectomy. RESULTS AND LIMITATIONS: 51.7% of patient samples showed positive KLK4::KLKP1 expression; more commonly in cores of PCa (38%) versus non-cancer (20.6%) (p < 0.0001) and in lower Gleason Grade Group tumors (1-3) vs (4-5). KLK4::KLKP1 expression positively correlated with ERG positivity and inversely associated with PTEN loss. No significant association was found with SPINK1 expression, seminal vesicle invasion, positive surgical margin, pathological stage, or patient age (< 50 or ≥ 50). The association between PTEN loss and BCR increased when combined with KLK4::KLKP1 negativity (HR 2.31, CI 1.03-5.20, p = 0.042). CONCLUSIONS: KLK4::KLKP1 expression is more common in this cohort of Middle Eastern men than has been reported in North American men. It is associated with ERG positivity and inversely correlated with PTEN loss. In isolation, KLK4::KLKP1 expression was not significantly associated with clinical outcome or pathological parameters. However, its expression is associated with certain molecular subtypes (ERG-positive, PTEN-intact) and as we demonstrate may help further stratify the risk of recurrence within these groups.
Authors: Richard Flavin; Andreas Pettersson; Whitney K Hendrickson; Michelangelo Fiorentino; Stephen Finn; Lauren Kunz; Gregory L Judson; Rosina Lis; Dyane Bailey; Christopher Fiore; Elizabeth Nuttall; Neil E Martin; Edward Stack; Kathryn L Penney; Jennifer R Rider; Jennifer Sinnott; Christopher Sweeney; Howard D Sesso; Katja Fall; Edward Giovannucci; Philip Kantoff; Meir Stampfer; Massimo Loda; Lorelei A Mucci Journal: Clin Cancer Res Date: 2014-03-31 Impact factor: 12.531
Authors: Ramy A Abdelsalam; Ibrahim Khalifeh; Alan Box; Maria Kalantarian; Sunita Ghosh; Hatem Abou-Ouf; Tamara Lotfi; Mohammed Shahait; Nallasivam Palanisamy; Tarek A Bismar Journal: J Cancer Res Clin Oncol Date: 2020-04-30 Impact factor: 4.553