%0 Journal Article %T The prognostic significance and value of cyclin D1, CDK4 and p16 in human breast cancer %A Emmi Peurala %A Peppi Koivunen %A Kirsi-Maria Haapasaari %A Risto Bloigu %A Arja Jukkola-Vuorinen %J Breast Cancer Research %D 2013 %I BioMed Central %R 10.1186/bcr3376 %X The material consisted of 102 formalin-fixed human breast cancer samples, in which cyclin D1, CDK4 and p16 expression was evaluated immunohistochemically. The amounts of cyclin D1 mRNA present were analyzed by quantitative real time PCR.High cyclin D1 expression statistically significantly correlated with lower tumor grade, estrogen and progesterone receptor positivity and lower proliferation activity in breast tumors and increased breast cancer-specific survival and overall survival. Tumors with high cyclin D1 protein had 1.8 times higher expression of cyclin D1 mRNA. CDK4 expression did not correlate with cyclin D1 expression or the survival data. p16 expression was associated with Human Epidermal Growth Factor Receptor 2 (HER2) negativity and increased breast cancer-specific survival and disease-free survival. No statistical correlations between cyclin D1, CDK4 and p16 were found.Cyclin D1 was associated with a good breast cancer prognosis but functioned independently of CDK4. High cyclin D1 expression may be partially due to increased CCND1 transcription. p16 correlated with a better prognosis and may function without CDK4. In conclusion, it appears that cyclin D1, CDK4 and p16 function independently in human breast cancer.The retinoblastoma tumor suppressor gene (RB) encodes a nuclear phosphoprotein that plays a central role in regulating the cell cycle [1]. RB regulates progression through the G1-to-S phase transition of the cell cycle [1]. Loss of RB is well documented in many human tumor types and it is probable that the p16-cyclin D1-CDK4/6-RB pathway is disrupted in most human malignancies [2]. Extracellular signals induce the expression of cyclin D1 in cells entering the cell cycle and this binds to and activates cyclin-dependent kinases (CDK4 and CDK6) (Figure 1) [1-5]. The ensuing complexes in turn lead to the phosphorylation of RB, resulting in its dissociation from the transcription factors, predominantly members of the E2F family, which then activate %U http://breast-cancer-research.com/content/15/1/R5