Expression of the G2-M checkpoint regulators cyclin B1 and P34(CDC2) in breast cancer: A correlation with cellular kinetics

In this study, the expression of cyclin BI and p34(cdc2) in neoplastic and non-neoplastic breast lesions was evaluated by immunohistochemistry and qua ntitative analysis in relation to cellular kinetic parameters such as Mitot ic Index (MI), Anatelophase Index (ATI), and Apoptotic Index (AI). The perc entage of cyclin B1 and p34(cdc2)-positive cells was significantly higher i n neoplastic glands than in their normal counterparts. This finding was par alleled by significantly higher values of MI, ATI, and AI in breast cancer than in normal glands. Furthermore, two groups with different cytokinetic c haracteristics were identified among infiltrating ductal carcinomas by an u nsupervised learning technique of cluster analysis using rite percentages o f cyclin BI and p34(cdc2) positive cells and the cellular kinetic parameter s (MI, ATI and AI) as variables. The final clusters, groups I and II, consi sted of 42 and 13 cases respectively. The first cluster (group I) was chara cterized by a significant linear correlation between the percentages of cyc lin B1 and p34(cdc2)-positive cells. On the contrary, the second cluster. ( group II) revealed no correlation between these two proteins and was charac terized by values of p34(cdc2) largely exceeding those of cyclin BI. A posi tive con elation between the expression of these two proteins and the cellu lar kinetic parameters (MI, ATI and AI) was also Sound in group I but not i n group II. These observations suggest that a disturbed nuclear translocati on of Mitosis Promoting Factor (MPF) components is present in group II case s, resulting in a defective cellular division cycle. In fact, group I cases showed lymph node metastasis more frequently than group II cases. Our resu lts suggest that the analysis of the cell cycle "machinery" components, suc h as the cyclins and their dependent kinases, can identify tumors with diff erent levels of aggressiveness.