F-Box protein p45SKP2 is the substrate-specific receptor of ubiquitin-protein ligase SCF/p45SKP2 and is involved in the degradation of p27Kip1 through the ubiquitin/proteasome pathway. In addition, p45SKP2 facilitates proteolysis of other molecules related to the cell cycle, is frequently over-expressed in transformed cells, and induces S phase in quiescent cells. The aim of this study was to determine whether p45SKP2 expression is altered in aggressive lesions of Kaposi's sarcoma and its relation to p27KIP1down-regulation. We performed immunohistochemistry using antibodies directed to p45SKP2, p27KIP1, and Ki67 on paraffin blocks corresponding to 47 cases of Kaposi's sarcoma (8 macules, 10 plaques, 12 tumors, and 15 extracutaneous lesions). p45SKP2 nuclear over-expression was present in all Kaposi's sarcoma stages, being significantly increased in skin tumors (mean ± 95% confidence interval: 39.2 ± 18.8) and extracutaneous lesions (25.8 ± 17.3) as compared with macules (18.9 ± 8.2) and plaques (29.2 ± 12.0; P = .0199). On the other hand, Kaposi's sarcoma progression was associated with a decrease in p27KIP1 expression and Ki67 immunoreactivity was independent of disease stage. No statistically significant differences were found in regard to patients' sex and human immunodeficiency virus status and regression analysis failed to show a correlation among p45SKP2, p27KIP1 and Ki67 immunostaining scores. These findings suggest that p45SKP2 is involved in Kaposi's sarcoma progression, not only by promoting the degradation of p27KIP1 but also through other mechanisms still unknown.
- Cell cycle
- Kaposi's sarcoma
- P27 , p45 , Proteasome, Ubiquitin KIP1 SKP2