title: Expression of CDK1(Tyr15), pCDK1(Thr161), Cyclin B1 (total) and pCyclin B1(Ser126) in vulvar squamous cell carcinoma and their relations with clinicopatological features and prognosis.
abstract: Cyclin B1-CDK1 complex plays an important role in the regulation of cell cycle. Activation of Cyclin B1 and CDK1 and the formation of the complex in G2/M are under multiple regulations involving many regulators such as isoforms of 14-3-3 and CDC25 and Wee1. Abnormal expression of Cyclin B1 and CDK1 has been detected in various tumors. However, to our knowledge no previous study has investigated Cyclin B1 and CDK1 in vulvar cancer. Therefore, we evaluated the statuses of CDK1Tyr15, pCDK1Thr161, Cyclin B1 (total) and pCyclin B1Ser126 in 297 cases of vulvar squamous cell carcinomas by immunohistochemistry. Statistical analyses were performed to explore their clinicopathological and prognostic values. In at least 25% of tumor cases high expression of CDK1Tyr15, pCDK1Thr161, Cyclin B1 (total) and pCyclin B1Ser126 was observed, compared to the low levels in normal vulvar squamous epithelium. Elevated levels of CDK1Tyr15, pCDK1Thr161, Cyclin B1 (total) and pCyclin B1Ser126 were correlated with advanced tumor behaviors and aggressive features. Although CDK1Tyr15, pCDK1Thr161, Cyclin B1 (total) and pCyclin B1Ser126 could not be identified as prognostic factors, combinations of (pCDK1Thr161 C+N + 14-3-3σN), (pCDK1Thr161 C+N + 14-3-3ηC), (pCDK1Thr161 C+N + Wee1C) and (pCDK1Thr161 C+N + 14-3-3σN + 14-3-3ηC + Wee1C) were correlated with disease-specific survival (p = 0.036, p = 0.029, p = 0.042 and p = 0.007, respectively) in univariate analysis. The independent prognostic significance of (pCDK1Thr161 C+N + 14-3-3σN + 14-3-3ηC + Wee1C) was confirmed by multivariate analysis. In conclusion, CDK1Tyr15, pCDK1Thr161, Cyclin B1 (total) and pCyclin B1Ser126 may be involved in progression of vulvar squamous cell carcinoma. The combination of pCDK1Thr161, 14-3-3σ, 14-3-3η and Wee1 was a statistically independent prognostic factor.
authors: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors: Zhihui
authors: Z
authors: Wang
authors: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors: Ana
authors: A
authors: Slipicevic
authors: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors: Mette
authors: M
authors: Førsund
authors: Department of Obstetrics and Gynecology, The Norwegian Radium Hospital, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors: Claes G
authors: CG
authors: Trope
authors: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors: Jahn M
authors: JM
authors: Nesland
authors: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors: Ruth
authors: R
authors: Holm
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016203:CDC2 Protein Kinase; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D056744:Cyclin B1 / Q000096:biosynthesis* / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics; D015996:Survival Rate; D014846:Vulvar Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology
chemical_list: C534699:CCNB1 protein, human; D056744:Cyclin B1; D009363:Neoplasm Proteins; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases