Overexpression of p27 protein in human breast cancer correlates with in vitro resistance to doxorubicin and mitomycin C.

ABSTRACT

BACKGROUND: The cycle regulatory protein p27, an inhibitor of cyclin-dependent kinase (CDK), has been attributed a role in resistance to cancer chemotherapy. However, the predictive value of p27 for chemosensitivity of breast cancer is still unclear. We therefore analyzed the in vitro chemosensitivity to a series of anticancer agents in fresh breast cancer specimens and correlated it with the respective expression levels of p27. MATERIALS AND METHODS: The expression of p27 protein was examined immunohistochemically in 119 patients with primary breast cancer. The in vitro chemosensitivity was assessed by the histoculture drug response assay (HDRA) using mitomycin C (MMC), 5-fluorouracil (5-Fu), Doxorubicin (DXR), cisplatin (CDDP) and cyclophosphamide (CPA). RESULTS: Fifty-six (47%) of the 119 patients demonstrated p27 overexpression. The susceptibility of DXR and MMC in tumors with high p27 expression was significantly higher than that in tumors with low p27 expression. CONCLUSION: Immunohistochemical results regarding p27 might be therapeutically useful as an indicator of response to DXR and/or MMC based adjuvant chemotherapy for breast cancer.