Cyclin D1-CDK4 complex, a possible critical factor for cell proliferation and prognosis in laryngeal squamous cell carcinomas

Cyclin D1 and its catalytic partner CDK4 are known to play important roles in the G(1)/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 immunohistochemic al expression of cyclin D1, CDK4 and proliferating cell nuclear antigen (PC NA) in 102 patients with laryngeal squamous cell carcinoma (LSCC), Cyclin D 1 overexpression was observed in 59 cases (57.8%) of LSCC, and was signific antly correlated with tumor site, tumor size, lymph node metastasis and adv anced 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 measur ed 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 signifi cantly associated with disease-free survival and overall survival, CDK4 ove rexpression 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 posse ss a significant prognostic role. By multivariate analysis, cyclin D1 overe xpression, lymph node metastasis and advanced stage were independent progno stic factors for disease-free survival. Cyclin D1 overexpression, CDK4 over expression, tumor grade, lymph node metastasis and advanced stage were inde pendent prognostic factors for overall survival. These findings indicate th at cyclin D1 and CDK4 overexpression and/or co-overexpression of these prot eins may play a pivotal role in the biological behavior of LSCC and may pro vide a strong prognostic implication, (C) 2001 Wiley-Liss, Inc.