Abstract
Backgroundp27Kip1 plays a major role as a negative regulator of the cell cycle. The regulation of p27Kip1 degradation is mediated by its specific ubiquitin ligase subunits S-phase kinase protein (Skp) 2 and cyclin-dependent kinase subunit (Cks) 1. However, little is known regarding the prognostic utility of p27Kip1, Skp2 and Cks1 expression in renal cell carcinoma.MethodsImmunohistochemistry was performed for p27Kip1, Skp2 and Cks1 in tissue microarrays of 482 renal cell carcinomas with follow-up. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were also performed to determine their prognostic significance.ResultsImmunoreactivity of p27Kip1, Skp2 and Cks1 was noted in 357, 71 and 82 patients, respectively. Skp2 and Cks1 expression were not noted in chromophobe cancers. A strong correlation was found between Skp2 and Cks1 expression (P < 0.001), both of which were inversely related to p27Kip1 levels (P = 0.006 and P < 0.001), especially in primary and clear-cell cancers. Low p27Kip1 expression and Skp2 expression were correlated with larger tumor size and higher stage, as well as tumor necrosis. Cks1 expression was only correlated with tumor size. In univariate analysis, low p27Kip1 expression, Skp2 and Cks1 expression were all associated with a poor prognosis, while in multivariate analysis, only low p27Kip1 expression were independent prognostic factors for both cancer specific survival and recurrence-free survival in patients with RCC.ConclusionOur results suggest that immunohistochemical expression levels of p27Kip1, Skp2 and Cks1 may serve as markers with prognostic value in renal cell carcinoma.
Highlights
Renal cell carcinoma (RCC) is the most common malignancy in adult kidney, with 30,000 new cases per year in the U.S and 20,000 cases in the European Union [1]
A strong correlation was found between Skp2 and Cks1 expression (P < 0.001), both of which were inversely related to p27Kip1 levels (P = 0.006 and P < 0.001), especially in primary and clear-cell cancers
Our results suggest that immunohistochemical expression levels of p27Kip1, Skp2 and Cks1 may serve as markers with prognostic value in renal cell carcinoma
Summary
Renal cell carcinoma (RCC) is the most common malignancy in adult kidney, with 30,000 new cases per year in the U.S and 20,000 cases in the European Union [1]. Over the last 20 years, the incidence of renal cell carcinoma in the two regions has increased by 30% [2]. Though the number of RCC cases in Asian is still unknown, publications in this regard have suggested a tendency of annual increase. In light of this situation, predicting the prognosis of RCC patients becomes essential for planning and optimizing treatment strategies. The prognosis of RCC is usually affected by such factors as per-. There lies the possibility that biologic markers, which have associated with tumor progression, could serve as accurate prognostic markers or targets for specific intervention
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