Transcriptional complementarity in breast cancer: Application to detectionof circulating tumor cells

Background: We used a combination of genetic subtraction, silicon DNA micro array analysis, and quantitative PCR to identify tissue- and tumor-specific genes as diagnostic targets for breast cancer. Methods and Results: From a large number of candidate antigens, several spe cific subsets of genes were identified that showed concordant and complemen tary expression profiles. Whereas transcriptional profiling of mammaglobin resulted in the detection of 70% of tumors in a panel of 46 primary and met astatic breast cancers, the inclusion of three additional markers resulted in detection of all 46 specimens. Immunomagnetic epithelial cell enrichment of circulating tumor cells from the peripheral blood of patients with meta static breast cancer, coupled with RT PCR-based amplification of breast tum or-specific transcripts, resulted in the detection of anchorage-independent tumor cells in the majority of patients with breast cancer with known meta static disease. Conclusion: Complementation of mammaglobin with three additional genes in R T-PCR increases the detection of breast cancers in tissue and circulating t umor cells.