Evaluation of a Panel of Tumor Markers for Molecular Detection of Circulating Cancer Cells in Women with Suspected Breast Cancer

Abstract

Purpose: We examined the feasibility of using molecular characterization of circulating tumor cells as a method for early detection of breast cancer. Research Design: Women without a prior history of cancer who had a breast abnormality detected on imaging followed by a breast biopsy were enrolled in this study. Density gradient centrifugation and immunomagnetic capture were used to enrich for epithelial cells from f20 mL of blood. Real-time reverse transcription-PCR was used to quantitate the expression levels of the highly breast-specific genes, mammaglobin, c-aminobutyric acid type A receptor p subunit (GABA A p ), B305D-C, and B726P in the epithelial cell^enriched samples. Results: The assay was technically feasible in 154 of 199 accrued patients. From their clinical assessment, 100 patients had benign breast disease, 10 patients had ductal carcinoma in situ, and 44 patients had invasive breast cancer. We constructed a diagnostic test that classified patients with mammaglobin levels of at least 32.2 copies/pg h-actin (units) in their circulating epithelial cells as positive for invasive breast cancer. This resulted in a sensitivity and specificity of 63.3% and 75.0%, respectively. A diagnostic test that classified patients as positive for invasive breast cancer when either mammaglobin levels were >46.3 units or B305D-C levels were >11.6 units increased the sensitivity and specificity to 70.5% and 81.0%, respectively. In the latter test, 12 of the 14 node-positive breast cancer patients were correctly identified. Including GABA A p and B726P in the test did not increase its diagnostic potential. Conclusions: These results suggest that molecular characterization of circulating epithelial cells using mammaglobin and B305D-C offers potential for early detection of invasive breast cancer.

GABA(A) Receptor Pi (GABRP) Stimulates Basal-like Breast Cancer Cell Migration through Activation of Extracellular-regulated Kinase 1/2 (ERK1/2)

“…Taken together with the correlation of GABRP with the BLBC subtype, metastatic spread to the brain, overall patient survival, and the migratory ability of BLBC cells described herein, GABRP may be a viable therapeutic target for treating BLBC. Supporting this possibility, GABRP is consistently detected in circulating breast tumor cells (51)(52)(53)(54) and in lymph nodes isolated from breast cancer patients (55). Targeting GABRP should be achievable because it is a cell surface receptor subunit.…”

Evaluation of a RT-PCR based routine screening tool for the detection of disseminated epithelial cells in the bone marrow of breast cancer patients

“…Recently, RT-PCR based methods have been established as an alternative to ICC. Various markers were evaluated including mammaglobin and cytokeratin 19 (CK19) [8][9][10][11][12][13]. CK19 is an intermediate filament cytokeratin and stably expressed in epithelial tissues but not in mesenchymal haemopoietic cells.…”

Development of a high‐throughput membrane‐array method for molecular diagnosis of circulating tumor cells in patients with gastric cancers

“…According to several recent studies, [34][35][36] the use of a panel of molecular markers provides a more sensitive method for the detection of several human malignancies including colorectal cancer, lung cancer and breast cancer. In the present study, we demonstrated that with combination of 4 mRNA markers, expression of any 3 mRNA markers could achieve the highest diagnostic accuracy (90.3%) in discrimination between GC patients and normal persons, with sensitivity of 89.1% and specificity of 91.3%, whereas 4 detectable mRNA markers were an independently unfavorable prognostic predictor for GC patients postoperatively.…”