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Detection of Circulating Breast Tumor Cells by Differential Expression of Marker Genes¹

Division of Experimental Therapy [A. J. B., B. W., A. C. L., L. J. v. V.] and Departments of Pathology [R. P., L. J. v. V.], Radiotherapy [A. A. M. H.], and Medical Oncology [S. R.], The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands, and Department of Immunotherapy, Central Laboratory of Blood Transfusion and Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the Netherlands [O. J. H. M. V.]

Purpose: We undertook a systematic approach to identify breast cancer (BC) marker genes with molecular assays and evaluated these marker genes for the detection of minimal residual disease in peripheral blood mononuclear cells (PBMCs).

Experimental Design: We used serial analysis of gene expression to identify a range of genes that were expressed in BC but absent in the expression profiles of blood and bone marrow cells. Next, we evaluated a panel of four marker genes (p1B, PS2, CK19, and EGP2) by real-time quantitative PCR in 103 PBMC samples from patients with metastatic BC (stage III/IV) and in 96 PBMC samples from healthy females.

Results: Increased marker gene expression of at least one marker was seen in 33 of 103 patients. Using quadratic discriminant analysis including all four marker genes, we determined a discriminant value with 29% positivity in the BC patient group that did not yield false positive results among the healthy females.

Conclusions: Real-time PCR for the simultaneous expression of multiple cancer-specific genes may ensure the specificity required for the clinical application of mRNA expression-based assays for occult tumor cells.

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