ABSTRACT
BACKGROUND: Gene expression of peripheral myelin protein 22 (PMP22) and the epithelial membrane proteins (EMPs) was found to be differentially expressed in invasive and non-invasive breast cell lines in a previous study. We want to evaluate the prognostic impact of the expression of these genes on breast cancer. METHODS: In a retrospective multicenter study, gene expression of PMP22 and the EMPs was measured in 249 primary breast tumors by real-time PCR. Results were statistically analyzed together with clinical data. RESULTS: In univariable Cox regression analyses PMP22 and the EMPs were not associated with disease-free survival or tumor-related mortality. However, multivariable Cox regression revealed that patients with higher than median PMP22 gene expression have a 3.47 times higher risk to die of cancer compared to patients with equal values on clinical covariables but lower PMP22 expression. They also have a 1.77 times higher risk to relapse than those with lower PMP22 expression. The proportion of explained variation in overall survival due to PMP22 gene expression was 6.5% and thus PMP22 contributes equally to prognosis of overall survival as nodal status and estrogen receptor status. Cross validation demonstrates that 5-years survival rates can be refined by incorporating PMP22 into the prediction model. CONCLUSIONS: PMP22 gene expression is a novel independent prognostic factor for disease-free survival and overall survival for breast cancer patients. Including it into a model with established prognostic factors will increase the accuracy of prognosis.
Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Breast Neoplasms/mortality , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/mortality , Carcinoma, Lobular/genetics , Carcinoma, Lobular/mortality , Myelin Proteins/genetics , Austria , Biomarkers, Tumor/analysis , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/pathology , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Membrane Glycoproteins/genetics , Middle Aged , Neoplasm Staging , Prognosis , Proportional Hazards Models , Receptors, Estrogen/analysis , Receptors, Estrogen/genetics , Reproducibility of Results , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Risk Assessment , Risk Factors , Survival Rate , Time FactorsABSTRACT
OBJECTIVE: Metastatic relapse due to early dissemination of tumor cells is associated with poor prognosis for epithelial cancer. The molecular characterization of these single cells or cell clusters that have evaded the tumor is indispensable in order to evaluate their biological behavior and metastatic potential. In this study, we established a sensitive immunomagnetic method to isolate rare cancer cells from peripheral blood based on their expression of epithelial- or tumor-cell-specific markers. METHODS: Low numbers of cells of breast cancer cell lines - ZR-75-1, MCF-7, HBL-100 - were spiked into peripheral blood specimens of healthy volunteers. Enrichment of tumor cells was performed using either pre-coupled HEA and/or ErbB2 microbeads or a mixture of three monoclonal antibodies against HEA, ErbB2 and EGFR. RESULTS: The recovery rate of spiked tumor cells correlated with the expression of the corresponding antigens. ZR-75-1 cells high expressing all three genes could be isolated to 60-71%. MCF-7 cells, which hardly express EGFR, showed a significant better recovery by using two specific antibodies in combination (50-68%) than one pre-coupled bead alone (31-42%). HBL-100 cells little expressing HEA could not be isolated with HEA microbeads and only to 27% in combination with ErbB2 beads -in contrast the use of an antibody cocktail achieved 38%. CONCLUSION: As tumor and epithelial specific cell marker antigens are expressed differently in disseminated tumor cells, the immunomagnetic enrichment from peripheral blood is most robust and reliable when using a combination of specific antibodies compared to single antibodies.
Subject(s)
Antibodies, Monoclonal/immunology , Breast Neoplasms/blood , Immunomagnetic Separation/methods , Neoplastic Cells, Circulating/pathology , Adult , Antigens, Neoplasm/biosynthesis , Antigens, Neoplasm/immunology , Breast Neoplasms/immunology , Breast Neoplasms/pathology , Cell Adhesion Molecules/biosynthesis , Cell Adhesion Molecules/immunology , Cell Line, Tumor , Epithelial Cell Adhesion Molecule , ErbB Receptors/biosynthesis , ErbB Receptors/immunology , Humans , Microspheres , Neoplastic Cells, Circulating/immunology , Receptor, ErbB-2/biosynthesis , Receptor, ErbB-2/immunology , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
BACKGROUND: This study evaluated serum vascular endothelial growth factor (VEGF) levels in women with abnormal intrauterine and ectopic pregnancies (EP) at 6 weeks gestation. METHODS: We conducted a prospective case-control study comparing serum VEGF concentrations among 84 women with abnormal intrauterine and EP matched for gestational age (42 women in each group). We analysed whether serum VEGF levels >200 pg/ml would discriminate between abnormal intrauterine pregnancies and EP at 6 weeks gestation, and we calculated sensitivity, specificity and positive predictive values. RESULTS: Serum VEGF concentrations did not show statistically significant differences between women with abnormal intrauterine pregnancies (median, 198.5 pg/ml; range, 0-701.6) and EP (median, 211.2 pg/ml; range 0-628.8). When threshold concentrations of a serum VEGF level >200 pg/ml were used, abnormal intrauterine pregnancy could be distinguished from EP with a sensitivity of 56%, a specificity of 51%, and a positive predictive value of 53%. CONCLUSIONS: VEGF does not discriminate ectopic from abnormal intrauterine pregnancies at 6 weeks gestation, and thus should not be used in clinical management.
