Expression Profiles of Retinoblastoma Protein and p27Kip1 According to HER2 Amplification Status in Primary Breast Cancer

Abstract

Purpose: Human epidermal growth factor receptor-2 (HER2)/neu amplification affects the cell proliferation through the modulation of multiple G1 cell cycle regulators in breast tumor cells. We performed this study to investigate whether retinoblastoma protein (pRB) and p27Kip1 were differently expressed according to the HER2 amplification status in human breast cancer. Methods: HER2 amplification was assayed by fluorescence in situ hybridization and the expression of cell cycle regulators were assayed by immunohistochemistry on 153 consecutive invasive breast cancers. The proliferative activity of breast cancer was analyzed according to the HER2 amplification and cell cycle protein expression status. Results: HER2 amplification was observed in 39 (25.5%) of 153 breast cancers. In the HER2 amplified breast cancers, the pRB expression was significantly increased (p=0.011) whereas there was no significant relationship between HER2 amplification and p27Kip1 expression. There was an inverse correlation between pRB expression and Ki67 labeling index in the HER2 amplified breast cancers (p= 0.036). In contrast, Ki-67 labeling index was significantly decreased as p27Kip1 expression increased in HER2 nonamplified breast cancers (p=0.028). In HER2 non-amplified breast cancers, we could not observe any association between the pRB expression and Ki67 labeling index. Conclusion: The proliferation of the breast cancers was associated with pRB expression in HER2 amplified tumors whereas it was associated with p27Kip1 expression in HER2 non-amplified tumors. The results of the current study indicate that the cell proliferative activity of the breast cancer is under different growth signal pathways according to HER2 amplification status.