Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Department of Obstetrics and Gynecology, The Norwegian Radium Hospital, Oslo University Hospital and University of Oslo, Oslo, Norway.
PLoS One. 2015 Apr 7;10(4):e0121398. doi: 10.1371/journal.pone.0121398. eCollection 2015.
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.
细胞周期蛋白 B1-CDK1 复合物在细胞周期调控中起着重要作用。Cyclin B1 和 CDK1 的激活以及 G2/M 期复合物的形成受到多种调节因子的影响，包括 14-3-3 和 CDC25 同工型和 Wee1。在各种肿瘤中已经检测到 Cyclin B1 和 CDK1 的异常表达。然而，据我们所知，以前没有人研究过外阴癌中的 Cyclin B1 和 CDK1。因此，我们通过免疫组织化学法评估了 297 例外阴鳞状细胞癌中 CDK1Tyr15、pCDK1Thr161、Cyclin B1（总）和 pCyclin B1Ser126 的状态。进行了统计学分析以探讨它们的临床病理和预后价值。与正常外阴鳞状上皮中的低水平相比，至少 25%的肿瘤病例中观察到 CDK1Tyr15、pCDK1Thr161、Cyclin B1（总）和 pCyclin B1Ser126 的高表达。CDK1Tyr15、pCDK1Thr161、Cyclin B1（总）和 pCyclin B1Ser126 的升高水平与晚期肿瘤行为和侵袭性特征相关。尽管 CDK1Tyr15、pCDK1Thr161、Cyclin B1（总）和 pCyclin B1Ser126 不能被确定为预后因素，但（pCDK1Thr161 C+N + 14-3-3σN）、（pCDK1Thr161 C+N + 14-3-3ηC）、（pCDK1Thr161 C+N + Wee1C）和（pCDK1Thr161 C+N + 14-3-3σN + 14-3-3ηC + Wee1C）的组合与疾病特异性生存相关（p=0.036，p=0.029，p=0.042 和 p=0.007）。（pCDK1Thr161 C+N + 14-3-3σN + 14-3-3ηC + Wee1C）的独立预后意义通过多变量分析得到证实。总之，CDK1Tyr15、pCDK1Thr161、Cyclin B1（总）和 pCyclin B1Ser126 可能参与了外阴鳞状细胞癌的进展。pCDK1Thr161、14-3-3σ、14-3-3η 和 Wee1 的组合是一个统计学上独立的预后因素。
