Abstract
The cyclin-dependent kinase inhibitor p27Kip1 is a negative regulator of cell proliferation. Its expression is known to be altered in a proteasome-dependent manner without changes in DNA level. Reduced expression of p27Kip1 is associated with aggressive behavior in a variety of human cancers. We investigated expression of p27Kip1 protein in human breast cancer using immunohistochemistry to assess its biologic implication along with cell-cycle analysis by flow cytometry. A total of 68 patients with invasive ductal cancer received adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-FU every 3 weeks for six cycles. In epithelial cells of normal and benign breast disease, expression of p27Kip1 was well preserved while its expression markedly decreased in breast cancer (45 of 68). Expression of p27Kip1 is significantly reduced in poorly differentiated cancers and in the advanced stage of the disease. Levels of p27Kip1 expression correlated with cell populations in G0/G1 phase of the cell cycle. In survival analysis, p27Kip1 was useful to predict disease free survival but not overall survival of the patients after adjuvant chemotherapy. In summary, p27Kip1 seems to have a role in the cell proliferation and differentiation process during carcinogenesis of breast cancer. The results of the present study suggest that p27Kip1 can be used in predicting response to systemic chemotherapy in a subset of patients with breast cancer.
MeSH terms
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Adult
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Aged
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Antineoplastic Combined Chemotherapy Protocols / pharmacology
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Breast Neoplasms / drug therapy
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Breast Neoplasms / genetics*
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Breast Neoplasms / mortality
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Breast Neoplasms / pathology
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Carcinoma, Ductal, Breast / drug therapy
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Carcinoma, Ductal, Breast / genetics*
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Carcinoma, Ductal, Breast / mortality
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Carcinoma, Ductal, Breast / pathology
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Cell Cycle
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Cell Cycle Proteins*
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Cell Differentiation / drug effects
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Cell Division / drug effects
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Chemotherapy, Adjuvant
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Combined Modality Therapy
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclophosphamide / administration & dosage
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Disease-Free Survival
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Female
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Fluorouracil / administration & dosage
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Gene Expression Regulation, Neoplastic* / drug effects
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Humans
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Mastectomy
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Methotrexate / administration & dosage
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Microtubule-Associated Proteins / biosynthesis
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Microtubule-Associated Proteins / deficiency*
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / physiology
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Middle Aged
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Neoplasm Metastasis
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / deficiency*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology
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Ploidies
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Receptors, Estrogen / analysis
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Receptors, Progesterone / analysis
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Risk Factors
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Survival Analysis
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Tumor Suppressor Proteins*
Substances
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Cell Cycle Proteins
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Microtubule-Associated Proteins
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Neoplasm Proteins
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Receptors, Estrogen
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Receptors, Progesterone
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Tumor Suppressor Proteins
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclophosphamide
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Fluorouracil
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Methotrexate