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.

Chemotherapy Enhances Cross-Presentation of Nuclear Tumor Antigens

“…Because our B16 tumors (H-2 b ) lacked the relevant restriction element (H-2 d ) for recognition by the CL4 TCR, we could rule out direct presentation of the antigen by the tumors [33] or by MHC-peptide exchange; a phenomenon described as “cross dressing” [20]. Thus in tumor-bearing C57BL/6 x BALB/C F 1 mice (H-2 bxd ), the proliferation of adoptively transferred H-2 d restricted CL4-TCR transgenic CD8 T cells could only be induced when F1 host APCs cross-present CL4 antigen.…”

“…Many of the tumor-associated antigen (TAAs) currently targeted in anti-tumor immunotherapy, such as survivin, MAGE-A10, and WT1, are predominantly expressed in the nucleus [12]–[14]. Moreover, several clinical studies have correlated the nuclear localization of different TAAs with poor clinical outcome in a variety of cancer types [15]–[20]. Therefore, it is important to understand the relative availability for cross-presentation of antigens in the nuclear compartment compared to other cellular compartments.…”

Clinical Significance of Survivin Expression in Patients with Urothelial Carcinoma

“…In addition, some immunohistochemistry (IHC) studies reported survivin expression in a high proportion of UC patients [18, 19]. In another study, survivin expression was observed in tumor cells, but not in normal urothelial cells, in patients with superficial bladder cancer [20, 21].…”

Drug priming enhances radiosensitivity of adamantinomatous craniopharyngioma via downregulation of survivin

“…Nuclear localization such as we observed in ACP is described to be a negative prognostic factor in non-small cell lung cancer, 20 laryngeal cancer, 43 and urothelial carcinoma, 34 where it was associated with invasion, progression, and worse prognosis as well as higher recurrence rates. In contrast, colon carcinoma demonstrated better outcome if survivin was present in the nucleus.…”