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.
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.
Urol Oncol. 2015 Jul 27. pii: S1078-1439(15)00325-7. doi: 10.1016/j.urolonc.2015.06.016. [Epub ahead of print]
Mathieu R1, Klatte T2, Margulis V3, Karam JA4, Rouprêt M5, Seitz C2, Karakiewicz PI6, Fajkovic H2, Wood CG4, Weizer AZ7, Raman JD8, Remzi M2, Rioux-Leclercq N9, Haitel A10, Bensalah K11, Lotan Y3, Rink M12, Kluth LA12, Scherr DS13, Robinson BD14, Shariat SF15.
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