Reduced Expression of p27 Correlates with High Grade Malignancy and is Associated with Poor Clinical Outcome in Human Greast Cancer / 대한암학회지

ABSTRACT

PURPOSE: The cyclin-dependent kinase inhibitor p27Kipl is a negative regulator of cell proliferation. Its expression is known to be altered in proteasome-dependent manner without changes in DNA level. Reduced expression of p27Kipl is associated with aggressive behavior in a variety of human cancers. We investigated expression of p27Kipl protein in human breast cancer using immunohistochemistry to assess its biologic implication along with cell cycle analysis by flow cytometry. MATERIALS AND METHODS: We peformed immunohistochemical assay for expression of p27 in total 68 patients with invasive ductal cancer along with 27 benign ductal hyperplasia and 10 ductal carcinoma in situ. The data were analyzed in association with proliferative activity of the same tissues and biologic parameters. RESULTS: In epithelial cells of normal and benign breast disease, expression of p27Kipl was well preserved while its expression markedly decreased in breast cancer (45 of 68). Expression of p27Kipl was significantly reduced in poorly differentiated cancers and in advanced stage of the disease. Levels of p27Kipl expression correlated with cell populations in GO/Gl phase of the cell cycle. In survival analysis, p27Kipl was useful to predict disease-free survival but not overall survival of the patients after adjuvant chemotherapy. CONCLUSION: p27Kipl seems to have a role in cell proliferation and differentiation process during carcinogenesis of breast cancer. The results of present study suggest that p27Kipl can be used in predicting response to systemic chemotherapy in a subset of patients with breast cancer.