Romain Mathieu1, Tobias Klatte2, Vitaly Margulis3, Jose A Karam4, Morgan Rouprêt5, Christian Seitz2, Pierre I Karakiewicz6, Harun Fajkovic2, Christopher G Wood4, Alon Z Weizer7, Jay D Raman8, Mesut Remzi2, Nathalie Rioux-Leclercq9, Andrea Haitel10, Karim Bensalah11, Yair Lotan3, Michael Rink12, Luis A Kluth12, Douglas S Scherr13, Brian D Robinson14, Shahrokh F Shariat15. 1. Department of Urology, Medical University Vienna, General Hospital, Vienna, Austria; Department of Urology, Rennes University Hospital, Rennes, France. 2. Department of Urology, Medical University Vienna, General Hospital, Vienna, Austria. 3. Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX. 4. Department of Urology, MD Anderson Cancer Center, Houston, TX. 5. 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. 6. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada. 7. Department of Urology, University of Michigan Cancer Center, Ann Arbor, MI. 8. Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA. 9. Department of Pathology, Rennes University Hospital, Rennes, France. 10. Department of Pathology, Medical University Vienna, Vienna, Austria. 11. Department of Urology, Rennes University Hospital, Rennes, France. 12. Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 13. Department of Urology, Weill Cornell Medical College, New York, NY. 14. Department of Urology, Weill Cornell Medical College, New York, NY; Department of Pathology, Weill Cornell Medical College, New York, NY. 15. Department of Urology, Medical University Vienna, General Hospital, Vienna, Austria; Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX; Department of Urology, Weill Cornell Medical College, New York, NY. Electronic address: shahrokh.shariat@meduniwien.ac.at.
Abstract
OBJECTIVE: Several small single-center studies have reported conflicting results on the prognostic value of survivin expression in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy. We attempted to validate the prognostic utility of survivin using a large multi-institutional cohort. MATERIAL AND METHODS: Survivin expression was evaluated by immunohistochemistry in tumor tissue from 732 patients with unilateral, sporadic UTUC treated with radical nephroureterectomy between 1990 and 2008 at 7 centers. Survivin expression was considered altered when at least 10% of the tumor cells stained positive. Associations of altered survivin expression with recurrence-free survival (RFS) and cancer-specific survival (CSS) were evaluated using Cox proportional hazards regression models. RESULTS: Altered survivin expression was observed in 288 (39.3%) tumors and was associated with more advanced pathological tumor stages (P<0.001), lymph node metastases (P<0.001), lymphovascular invasion (P<0.001), tumor necrosis (P = 0.027), and tumor architecture (P<0.001). Median follow-up was 35 (16-64) months. There were 191 (25.4%) patients who experienced disease recurrence, and 165 patients (21.9%) died of the disease. In the univariable analysis, altered survivin expression was significantly associated with worse RFS and CSS (each P<0.001); however, altered survivin expression did not achieve independent predictive status on multivariable models (P = 0.24 and P = 0.53). Similarly, survivin was not independently associated with outcomes in subgroup analyses, including patients with high-grade tumors. CONCLUSIONS: In UTUC, altered survivin expression is associated with worse clinicopathological features and worse RFS and CSS. However, it does not appear to be independently associated with cancer outcomes when considering standard prognostic factors.
OBJECTIVE: Several small single-center studies have reported conflicting results on the prognostic value of survivin expression in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy. We attempted to validate the prognostic utility of survivin using a large multi-institutional cohort. MATERIAL AND METHODS: Survivin expression was evaluated by immunohistochemistry in tumor tissue from 732 patients with unilateral, sporadic UTUC treated with radical nephroureterectomy between 1990 and 2008 at 7 centers. Survivin expression was considered altered when at least 10% of the tumor cells stained positive. Associations of altered survivin expression with recurrence-free survival (RFS) and cancer-specific survival (CSS) were evaluated using Cox proportional hazards regression models. RESULTS: Altered survivin expression was observed in 288 (39.3%) tumors and was associated with more advanced pathological tumor stages (P<0.001), lymph node metastases (P<0.001), lymphovascular invasion (P<0.001), tumor necrosis (P = 0.027), and tumor architecture (P<0.001). Median follow-up was 35 (16-64) months. There were 191 (25.4%) patients who experienced disease recurrence, and 165 patients (21.9%) died of the disease. In the univariable analysis, altered survivin expression was significantly associated with worse RFS and CSS (each P<0.001); however, altered survivin expression did not achieve independent predictive status on multivariable models (P = 0.24 and P = 0.53). Similarly, survivin was not independently associated with outcomes in subgroup analyses, including patients with high-grade tumors. CONCLUSIONS: In UTUC, altered survivin expression is associated with worse clinicopathological features and worse RFS and CSS. However, it does not appear to be independently associated with cancer outcomes when considering standard prognostic factors.
Authors: Sang Hun Song; Chang Hee Ye; Sangchul Lee; Sung Kyu Hong; Seok-Soo Byun; Sang Eun Lee; Jong Jin Oh Journal: J Cancer Res Clin Oncol Date: 2019-09-09 Impact factor: 4.553
Authors: Ricardo L Favaretto; Stênio C Zequi; Renato A R Oliveira; Thiago Santana; Walter H Costa; Isabela W Cunha; Gustavo C Guimarães Journal: Int Braz J Urol Date: 2018 Jan-Feb Impact factor: 1.541
Authors: Ricardo L Favaretto; Atessa Bahadori; Romain Mathieu; Andrea Haitel; Bernhard Grubmüller; Vitaly Margulis; Jose A Karam; Morgan Rouprêt; Christian Seitz; Pierre I Karakiewicz; Isabela W Cunha; Stenio C Zequi; Christopher G Wood; Alon Z Weizer; Jay D Raman; Mesut Remzi; Nathalie Rioux-Leclercq; Solene Jacquet-Kammerer; Karim Bensalah; Yair Lotan; Alexander Bachmann; Michael Rink; Alberto Briganti; Shahrokh F Shariat Journal: World J Urol Date: 2016-04-29 Impact factor: 4.226