title: Prognostic significance of the F-box protein Skp2 expression in diffuse large B-cell lymphoma.
abstract: The F-box protein Skp2 positively regulates the G1-S transition by promoting degradation of the cyclin-dependent kinase inhibitor p27(kip1) (p27). Recent evidence has suggested an oncogenic role of Skp2 in not only carcinogenesis but also lymphomagenesis. In this study, we performed immunohistochemical analysis on the cell-cycle-associated proteins, Skp2, p27, and Ki-67, in 27 patients with de novo diffuse large B-cell lymphoma (DLBCL), evaluating the correlation between the clinical characteristics and expression levels of these proteins. The patients were classified into two groups according to the positivity for Skp2 expression: a high Skp2 expression group (>60% positive for Skp2 in lymphoma cells) and a low Skp2 expression group (< or = 60%). A high level of Skp2 expression significantly correlated with advanced clinical stage (P = 0.029), although the increase did not correlate with age, gender, LDH levels, presence of extranodal disease, or performance status and resulted in no correlation with the International Prognostic Index-based risk grading. However, it was noteworthy that the high Skp2 expression group demonstrated a significantly worse prognosis than the low Skp2 expression group (P = 0.0007). The expression level of Skp2 correlated with that of Ki-67 but not necessarily with that of p27. The p27 expression level did not correlate patients' prognosis. Taken together, it was suggested that Skp2 was a valuable and independent marker predicting the outcome in DLBCL.
authors.affiliation: Second Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Seki
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamura
authors.forename: Hironori
authors.initials: H
authors.lastname: Koga
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Yakushiji
authors.forename: Michitoshi
authors.initials: M
authors.lastname: Hashiguchi
authors.forename: Kohji
authors.initials: K
authors.lastname: Yoshimoto
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ogata
authors.forename: Rie
authors.initials: R
authors.lastname: Imamura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakashima
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kage
authors.forename: Takato
authors.initials: T
authors.lastname: Ueno
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D018797:Cell Cycle Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D016393:Lymphoma, B-Cell / Q000401:mortality / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D044786:S-Phase Kinase-Associated Proteins; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D044786:S-Phase Kinase-Associated Proteins; C413374:p27 antigen