Detection and characterization of circulating tumor cells in blood of primary breast cancer patients by RT-PCR and comparison to status of bone marrow disseminated cells.
BACKGROUND
The role of circulating tumor cells (CTCs) in blood of primary breast cancer patients is still under investigation. We evaluated the incidence of CTCs in blood, we evaluated the correlation between CTCs and disseminated tumor cells (DTCs) in the bone marrow (BM), and we characterized CTCs for the expression of HER2, the estrogen receptor (ER) and the progesterone receptor (PR).


METHODS
Blood of 431 patients with primary breast cancer were analyzed for EpCAM, MUC1 and HER2 transcripts with the AdnaTest BreastCancer (AdnaGen AG, Germany). Expression of the ER and PR was assessed in an additional RT-PCR. BM aspirates from 414 patients were analyzed for DTCs by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3.


RESULTS
DTCs were found in 107/414 patients (24%), CTCs were detected in 58/431 (13%) patients. DTCs were associated with PR status of the primary tumor (P = 0.04) and CTCs significantly correlated with nodal status (P = 0.04), ER (P = 0.05), and PR (P = 0.01). DTCs in the BM weakly correlated with CTCs (P = 0.05) in blood. Interestingly, the spread of CTCs was mostly found in triple-negative tumors (P = 0.01) and CTCs in general were mostly found to be triple-negative regardless of the ER, PR and HER2 status of the primary tumor.


CONCLUSIONS
(1) Due to the weak concordance between CTCs and DTCs the clinical relevance may be different. (2) The biology of the primary tumor seems to direct the spread of CTCs. (3) Since the expression profile between CTCs and the primary tumor differs, the consequence for the selection of adjuvant treatment has to be evaluated.
Fehm
Tanja
T
Department of Gynecology and Obstetrics, Calwer Strasse 7, University Hospital of Tuebingen, D-72076 Tuebingen, Germany. tanja.fehm@med.uni-tuebingen.de
Hoffmann
Oliver
O
Aktas
Bahriye
B
Becker
Sven
S
Solomayer
Erich F
EF
Wallwiener
Diethelm
D
Kimmig
Rainer
R
Kasimir-Bauer
Sabine
S
D000230:Adenocarcinoma / Q000097:blood / Q000473:pathology*; D000951:Antigens, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001853:Bone Marrow / Q000473:pathology*; D019046:Bone Marrow Neoplasms / Q000556:secondary* / Q000648:ultrastructure; D001943:Breast Neoplasms / Q000097:blood / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000032:analysis; D017024:Chemotherapy, Adjuvant; D000071858:Epithelial Cell Adhesion Molecule; D004967:Estrogens; D005260:Female; D006801:Humans; D007633:Keratins / Q000032:analysis; D018396:Mucin-1 / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis*; D018365:Neoplasm, Residual; D009376:Neoplasms, Hormone-Dependent / Q000097:blood / Q000737:chemistry / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000737:chemistry*; D014411:Neoplastic Stem Cells / Q000737:chemistry; D011374:Progesterone; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D004967:Estrogens; D007633:Keratins; D018396:Mucin-1; D009363:Neoplasm Proteins; D011374:Progesterone; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C499379:EPCAM protein, human; C060192:MUC1 protein, human; C508053:ERBB2 protein, human