title: Over-expression of p45(SKP2) in Kaposi's sarcoma correlates with higher tumor stage and extracutaneous involvement but is not directly related to p27(KIP1) down-regulation.
abstract: F-Box protein p45(SKP2) is the substrate-specific receptor of ubiquitin-protein ligase SCF/p45(SKP2) and is involved in the degradation of p27(Kip1) through the ubiquitin/proteasome pathway. In addition, p45(SKP2) 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 p45(SKP2) expression is altered in aggressive lesions of Kaposi's sarcoma and its relation to p27(KIP1)down-regulation. We performed immunohistochemistry using antibodies directed to p45(SKP2), p27(KIP1), and Ki67 on paraffin blocks corresponding to 47 cases of Kaposi's sarcoma (8 macules, 10 plaques, 12 tumors, and 15 extracutaneous lesions). p45(SKP2) 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 p27(KIP1) 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 p45(SKP2), p27(KIP1) and Ki67 immunostaining scores. These findings suggest that p45(SKP2) is involved in Kaposi's sarcoma progression, not only by promoting the degradation of p27(KIP1) but also through other mechanisms still unknown.
authors.affiliation: Department of Pathology, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
authors.forename: R M
authors.initials: RM
authors.lastname: Penin
authors.forename: M T
authors.initials: MT
authors.lastname: Fernandez-Figueras
authors.forename: L
authors.initials: L
authors.lastname: Puig
authors.forename: J
authors.initials: J
authors.lastname: Rex
authors.forename: C
authors.initials: C
authors.lastname: Ferrandiz
authors.forename: A
authors.initials: A
authors.lastname: Ariza
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000737:chemistry; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003593:Cytoplasm / Q000737:chemistry; D018450:Disease Progression; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008025:Ligases / Q000096:biosynthesis*; D009367:Neoplasm Staging; D012514:Sarcoma, Kaposi / Q000378:metabolism / Q000473:pathology*; D012720:Severity of Illness Index; D012867:Skin / Q000737:chemistry / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
chemical_list: D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D044767:Ubiquitin-Protein Ligases; D008025:Ligases