Dong Y, Sui L, Sugimoto K, Tai Y, Tokuda M
Department of Physiology, Kagawa Medical University, Kagawa, Japan.
Int J Cancer. 2001 Jul 20;95(4):209-15. doi: 10.1002/1097-0215(20010720)95:4<209::aid-ijc1036>3.0.co;2-r.
Cyclin D1 and its catalytic partner CDK4 are known to play important roles in the G1/S checkpoint of the cell cycle. The complex formed by CDK4 and cyclin D1 has been strongly implicated in the control of cell proliferation and prognoses in human malignancies. We investigated the immunohistochemical expression of cyclin D1, CDK4 and proliferating cell nuclear antigen (PCNA) in 102 patients with laryngeal squamous cell carcinoma (LSCC). Cyclin D1 overexpression was observed in 59 cases (57.8%) of LSCC, and was significantly correlated with tumor site, tumor size, lymph node metastasis and advanced stage. CDK4 overexpression was observed in 48 cases (47.1%), and was significantly correlated with tumor size and advanced stage. Cyclin D1 and CDK4 expression was significantly associated with cell proliferation measured by PCNA (r = 0.812, p < 0.0001 and r = 0.725, p < 0.0001, respectively). The Kaplan-Meier analysis showed that cyclin D1 overexpression was significantly associated with disease-free survival and overall survival. CDK4 overexpression was significantly associated with overall survival. When cyclin D1 and CDK4 are combined, the patients with co-overexpression of cyclin D1-CDK4 revealed the poorest overall survival. Additionally, in early-stage (I-II) cases, co-overexpression of cyclin D1-CDK4 was also revealed to possess a significant prognostic role. By multivariate analysis, cyclin D1 overexpression, lymph node metastasis and advanced stage were independent prognostic factors for disease-free survival. Cyclin D1 overexpression, CDK4 overexpression, tumor grade, lymph node metastasis and advanced stage were independent prognostic factors for overall survival. These findings indicate that cyclin D1 and CDK4 overexpression and/or co-overexpression of these proteins may play a pivotal role in the biological behavior of LSCC and may provide a strong prognostic implication.
已知细胞周期蛋白D1及其催化伴侣CDK4在细胞周期的G1/S检查点中发挥重要作用。CDK4与细胞周期蛋白D1形成的复合物与人类恶性肿瘤的细胞增殖控制和预后密切相关。我们研究了102例喉鳞状细胞癌（LSCC）患者中细胞周期蛋白D1、CDK4和增殖细胞核抗原（PCNA）的免疫组化表达。在59例（57.8%）LSCC病例中观察到细胞周期蛋白D1过表达，且与肿瘤部位、肿瘤大小、淋巴结转移和晚期显著相关。在48例（47.1%）病例中观察到CDK4过表达，且与肿瘤大小和晚期显著相关。细胞周期蛋白D1和CDK4的表达与通过PCNA测量的细胞增殖显著相关（分别为r = 0.812，p < 0.0001和r = 0.725，p < 0.0001）。Kaplan-Meier分析表明，细胞周期蛋白D1过表达与无病生存期和总生存期显著相关。CDK4过表达与总生存期显著相关。当细胞周期蛋白D1和CDK4联合检测时，细胞周期蛋白D1-CDK4共过表达的患者总生存期最差。此外，在早期（I-II期）病例中，细胞周期蛋白D1-CDK4共过表达也显示出显著的预后作用。通过多因素分析，细胞周期蛋白D1过表达、淋巴结转移和晚期是无病生存期的独立预后因素。细胞周期蛋白D1过表达、CDK4过表达、肿瘤分级、淋巴结转移和晚期是总生存期的独立预后因素。这些发现表明，细胞周期蛋白D1和CDK4的过表达和/或这些蛋白的共过表达可能在LSCC的生物学行为中起关键作用，并可能提供强有力的预后意义。
