Detection of circulating breast tumor cells by differential expression of marker genes.
OBJECTIVE
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).


METHODS
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.
Bosma
Astrid J
AJ
Division of Experimental Therapy, Department of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
Weigelt
Britta
B
Lambrechts
A Caro
AC
Verhagen
Onno J H M
OJ
Pruntel
Roelof
R
Hart
Augustinus A M
AA
Rodenhuis
Sjoerd
S
van 't Veer
Laura J
LJ
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001706:Biopsy; D001853:Bone Marrow / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D018365:Neoplasm, Residual / Q000097:blood* / Q000235:genetics / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012680:Sensitivity and Specificity; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D000071858:Epithelial Cell Adhesion Molecule; D011506:Proteins; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D007633:Keratins