title: S-phase kinase-associated protein 2 expression in laryngeal squamous cell carcinomas and its prognostic implications.
abstract: The F-box protein S-phase kinase-associated protein 2 (Skp2) positively regulates the G1-S transition by controlling the stability of several G1 regulators, such as the cell cycle inhibitor p27kip1. However, the clinical significance of Skp2 in patients with laryngeal squamous cell carcinoma (LSCC) remains unknown. In this study, a potential distribution of Skp2 in LSCC and its clinical implications was investigated by an immunohistochemical study. Overall, Skp2 overexpression was observed in 36.7% (37 of 102) patients and was significantly associated with lymph node metastasis (p=0.002) and was inversely associated with p27kip1 expression (p=0.026). Survival analysis using the Kaplan-Meier method showed that Skp2 overexpression was significantly associated with shorter disease-free and overall survival (p=0.0051 and p=0.0002, respectively). When Skp2 expression and p27kip1 expression were combined, patients with both Skp2 overexpression and reduced expression of p27kip1 revealed poorest disease-free and overall survival as compared to the other cases (p=0.0017 and p<0.0001, respectively). Additionally, in early stage (I, II) cases, Skp2 expression was also revealed to possess a significant prognostic factor in overall survival (p=0.0234), but not in disease-free survival (p=0.2055). By multivariate analysis using the Cox proportional hazards model, tumor grade, tumor size, clinical stage and Skp2 expression were independent prognostic factors both in disease-free and overall survival. These findings indicated that Skp2 expression was closely associated with tumor progression and represented an independent marker for prognosis of LSCC.
authors.affiliation: Department of Physiology, Kagawa Medical University, Kagawa 761-0793, Japan.
authors.forename: Youyi
authors.initials: Y
authors.lastname: Dong
authors.forename: Li
authors.initials: L
authors.lastname: Sui
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tokuda
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D016196:S Phase; D044786:S-Phase Kinase-Associated Proteins; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D044786:S-Phase Kinase-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27