Romain Mathieu1,2, Tobias Klatte1, Ilaria Lucca1,3, Aurélie Mbeutcha1, Christian Seitz1, Pierre I Karakiewicz4, Harun Fajkovic1, Maxine Sun4, Yair Lotan5, Douglas S Scherr6, Francesco Montorsi7, Alberto Briganti7, Morgan Rouprêt8, Vitaly Margulis5, Michael Rink9, Luis A Kluth9, Malte Rieken10, Lukas Kenner11,12,13, Martin Susani11, Brian D Robinson6,14, Evanguelos Xylinas15, Wolgang Loidl16, Shahrokh F Shariat1,5,6. 1. Department of Urology, General Hospital, Vienna, Austria. 2. Department of Urology, Rennes University Hospital, Rennes, France. 3. Department of Urology, Centre hospitalier universitaire vaudois, Lausanne, Switzerland. 4. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, QC, Canada. 5. Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA. 6. Department of Urology, Weill Cornell Medical College, New York, NY, USA. 7. Department of Urology, Vita-Salute San Raffaele University, Milan, Italy. 8. Academic Department of Urology, La Pitié-Salpetrière Hospital, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie, University Paris 6, Paris, France. 9. Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 10. Department of Urology, University Hospital Basel, Basel, Switzerland. 11. Clinical Institute of Pathology, Medical University Vienna, Vienna, Austria. 12. Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria. 13. Unit of Pathology of Laboratory Animals (UPLA), University of Veterinary Medicine Vienna, Vienna, Austria. 14. Department of Pathology, Weill Cornell Medical College, New York, NY, USA. 15. Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, Paris, France. 16. Department of Urology, Krankenhaus der Barmherzigen Schwestern, Linz, Austria.
Abstract
OBJECTIVE: To validate Caveolin-1 as an independent prognostic marker of biochemical recurrence (BCR) in a large multi-institutional cohort of patients with prostate cancer treated with radical prostatectomy (RP). PATIENTS AND METHODS: Caveolin-1 expression was evaluated by immunochemistry on a tissue microarray in 3 117 patients treated with RP for prostate cancer at five institutions. Univariable and multivariable Cox proportional hazards regression models assessed the association of Caveolin-1 status with BCR. Harrell's c-index quantified prognostic accuracy. RESULTS: Caveolin-1 was overexpressed in 644 (20.6%) patients and was associated with higher pathological Gleason sum (P = 0.002) and lymph node metastases (P = 0.05). Within a median (interquartile range) follow-up of 38 (21-66) months, 617 (19.8%) patients experienced BCR. Patients with overexpression of Caveolin-1 had worse BCR-free survival than those with normal expression (log-rank test, P = 0.004). Caveolin-1 was an independent predictor of BCR in multivariable analyses that adjusted for the effects of standard clinicopathological features (hazard ratio 1.21, P = 0.037). Addition of Caveolin-1 in a model for prediction of BCR based on these standard prognosticators did not significantly improve the predictive accuracy of the model. In subgroup analyses, Caveolin-1 was associated with BCR in patients with favourable pathological features (pT2pN0 and Gleason score = 6; P = 0.021). CONCLUSIONS: We confirmed that overexpression of Caveolin-1 is associated with adverse pathological features in prostate cancer and independently predicts BCR after RP, especially in patients with favourable pathological features. However, it did not add prognostically relevant information to established predictors of BCR, limiting its use in clinical practice.
OBJECTIVE: To validate Caveolin-1 as an independent prognostic marker of biochemical recurrence (BCR) in a large multi-institutional cohort of patients with prostate cancer treated with radical prostatectomy (RP). PATIENTS AND METHODS: Caveolin-1 expression was evaluated by immunochemistry on a tissue microarray in 3 117 patients treated with RP for prostate cancer at five institutions. Univariable and multivariable Cox proportional hazards regression models assessed the association of Caveolin-1 status with BCR. Harrell's c-index quantified prognostic accuracy. RESULTS:Caveolin-1 was overexpressed in 644 (20.6%) patients and was associated with higher pathological Gleason sum (P = 0.002) and lymph node metastases (P = 0.05). Within a median (interquartile range) follow-up of 38 (21-66) months, 617 (19.8%) patients experienced BCR. Patients with overexpression of Caveolin-1 had worse BCR-free survival than those with normal expression (log-rank test, P = 0.004). Caveolin-1 was an independent predictor of BCR in multivariable analyses that adjusted for the effects of standard clinicopathological features (hazard ratio 1.21, P = 0.037). Addition of Caveolin-1 in a model for prediction of BCR based on these standard prognosticators did not significantly improve the predictive accuracy of the model. In subgroup analyses, Caveolin-1 was associated with BCR in patients with favourable pathological features (pT2pN0 and Gleason score = 6; P = 0.021). CONCLUSIONS: We confirmed that overexpression of Caveolin-1 is associated with adverse pathological features in prostate cancer and independently predicts BCR after RP, especially in patients with favourable pathological features. However, it did not add prognostically relevant information to established predictors of BCR, limiting its use in clinical practice.
Authors: Thomas Gevaert; Yves-Rémi Van Eycke; Thomas Vanden Broeck; Hein Van Poppel; Isabelle Salmon; Sandrine Rorive; Frank Claessens; Dirk De Ridder; Christine Decaestecker; Steven Joniau Journal: Sci Rep Date: 2018-09-25 Impact factor: 4.379