Nuclear, but not cytoplasmic, localization of survivin as a negative prognostic factor for survival in upper urinary tract urothelial carcinoma

Abstract

Survivin, a member of the inhibitor of apoptosis protein gene family, inhibits apoptosis and promotes mitosis. We determined whether nuclear or cytoplasmic localization of survivin could predict survival of patients with upper urinary tract urothelial carcinoma (UUTUC). Immunohistochemical staining for survivin was carried out on archival specimens from 125 consecutive patients with UUTUC who underwent radical nephroureterectomy. Nuclear and cytoplasmic staining of survivin was scored and compared with clinicopathologic features and cancer-specific survival (CSS). Nuclear expression of survivin was significantly correlated with tumor grade (p < 0.001), lymphovascular invasion (p = 0.022) and poor survival with an estimated 5-year CSS probability of 54% for tumors with nuclear expression of survivin vs. 73% for those without nuclear expression of survivin (hazard ratio = 2.19; 95% confidence interval = 1.02-4.70; p = 0.043). The 5-year cancer-specific survival rates of patients with cytoplasmic survivin-negative and -positive tumors were 66 and 67%, respectively. There was no difference in survival between patients with cytoplasmic survivin-negative tumors and those with cytoplasmic survivin-positive tumors. Using univariate analysis, nuclear survivin expression, tumor grade, pathological T stage, pathological N stage, and lymphovascular invasion were the predictive variables for CSS. In contrast, cytoplasmic survivin expression had no prognostic relevance. These data suggest that nuclear accumulation of survivin represents biologic aggressiveness and that nuclear survivin is a negative prognostic marker in patients with resected UUTUC.