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Recent studies have shown that overexpression of S-phase kinase-associated protein 2 (Skp2) occurs in many cancers at an advanced stage. We examined the clinicopathologic significance and prognostic implication of Skp2 expression in pancreatic invasive ductal carcinoma.Tissue samples from 46 pancreatic carcinomas were examined immunohistochemically for Skp2. The proportion of constituent tumor cells with Skp2 expression was analyzed and classified as high-level nuclear expression when more than 20% of the cancer cells were positive, or low-level nuclear expression otherwise.High-level Skp2 overexpression was detected in 13 (28.3%) of the 46 tumors. The incidence of high-level Skp2 was correlated with higher histological grade (P = 0.0056), the extent of lymph node metastasis (P = 0.0086), the level of lymphatic permeation (P = 0.0024), and poorer patient outcome (P = 0.0189). Multivariate analysis showed that high-level Skp2 expression was an independent predictor of overall patient survival (P = 0.0140).It is suggested that examination of Skp2 expression might be clinically useful for prognostication in patients with pancreatic carcinoma and that Skp2 protein might be a novel therapeutic molecular target.