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.