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Prognostic relevance of P-glycoprotein expression in breast cancer. 1995

S C Linn, and G Giaccone, and P J van Diest, and W M Blokhuis, and P van der Valk, and C K van Kalken, and C M Kuiper, and H M Pinedo, and J P Baak
Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.

BACKGROUND P-glycoprotein (Pgp) expression has been reported to be associated with a poor prognosis in some malignancies such as neuroblastoma, soft tissue sarcoma and acute myeloid leukemia. The prognostic role of Pgp expression in breast cancer is still unclear. We investigated the expression of Pgp in primary and metastatic breast cancer tissues in relation to patient characteristics and treatment outcome. METHODS Pgp expression was evaluated in 92 primary and 12 metastatic breast cancers by the use of immunohisto/cytochemistry with three monoclonal antibodies (MAbs) (JSB-1, C219, MRK16), and an RNAse protection assay. Follow-up information was available for 77 primary breast cancer patients (median follow-up 42 months; range 2-63 months). RESULTS Concordance among the anti-Pgp MAbs varied, the highest being between JSB-1 and MRK16 (71%; p=0.002). Pgp expression was more frequent in metastatic disease (58%) than in primary breast cancer (29%) (JSB-1; p=0.055). Pgp expression as assessed with JSB-1 (univariate analysis; p<0.05) was associated with shorter overall survival (OS). Nineteen (21%) primary breast cancers had Pgp expression in fibroblasts in desmoplastic stroma and this did not correlate with Pgp expression in the tumor. The combination of Pgp-positive tumor cells and Pgp-expressing fibroblasts was the strongest prognostic factor for OS by multivariate analysis. Subgroup analysis suggested that Pgp expression was associated with a shorter OS in tamoxifen-treated patients, but not in those who received chemotherapy (most often CMF). CONCLUSIONS Pgp expression in tumor cells, and especially when accompanied by Pgp expression in fibroblasts in desmoplastic stroma, has prognostic value in primary breast cancer patients and is likely to be a marker of a more malignant phenotype. Pgp expression of tumor cells might play a role in tamoxifen resistance. These findings may have important implications for teh treatment of breast cancer patients, and warrant further prospective investigation in a larger patient population.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009362 Neoplasm Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Metastase,Metastasis,Metastases, Neoplasm,Metastasis, Neoplasm,Neoplasm Metastases,Metastases
D011379 Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D012044 Regression Analysis Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see LINEAR MODELS) the relationship is constrained to be a straight line and LEAST-SQUARES ANALYSIS is used to determine the best fit. In logistic regression (see LOGISTIC MODELS) the dependent variable is qualitative rather than continuously variable and LIKELIHOOD FUNCTIONS are used to find the best relationship. In multiple regression, the dependent variable is considered to depend on more than a single independent variable. Regression Diagnostics,Statistical Regression,Analysis, Regression,Analyses, Regression,Diagnostics, Regression,Regression Analyses,Regression, Statistical,Regressions, Statistical,Statistical Regressions
D001940 Breast In humans, one of the paired regions in the anterior portion of the THORAX. The breasts consist of the MAMMARY GLANDS, the SKIN, the MUSCLES, the ADIPOSE TISSUE, and the CONNECTIVE TISSUES. Breasts
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D005260 Female Females
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D005500 Follow-Up Studies Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. Followup Studies,Follow Up Studies,Follow-Up Study,Followup Study,Studies, Follow-Up,Studies, Followup,Study, Follow-Up,Study, Followup

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