Original Paper

Histochemistry and Cell Biology

, Volume 123, Issue 6, pp 631-637

First online:

Characterisation of disseminated tumor cells in the bone marrow of breast cancer patients by the Thomsen–Friedenreich tumor antigen

  • Christian SchindlbeckAffiliated withFirst Department of Obstetrics and Gynecology, Ludwig Maximilians University of Munich Email author 
  • , Udo JeschkeAffiliated withFirst Department of Obstetrics and Gynecology, Ludwig Maximilians University of Munich
  • , Sandra SchulzeAffiliated withFirst Department of Obstetrics and Gynecology, Ludwig Maximilians University of Munich
  • , Uwe KarstenAffiliated withMax-Delbrück-Center for Molecular Medicine Berlin-Buch
  • , Wolfgang JanniAffiliated withFirst Department of Obstetrics and Gynecology, Ludwig Maximilians University of Munich
  • , Brigitte RackAffiliated withFirst Department of Obstetrics and Gynecology, Ludwig Maximilians University of Munich
  • , Harald SommerAffiliated withFirst Department of Obstetrics and Gynecology, Ludwig Maximilians University of Munich
  • , Klaus FrieseAffiliated withFirst Department of Obstetrics and Gynecology, Ludwig Maximilians University of Munich

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

The detection of disseminated tumor cells in the bone marrow (DTC-BM) of breast cancer patients has proved prognostic significance in all stages of the disease. Further characterisation of those cells could help to improve the biological understanding of metastases, develop targeted therapies and define surface markers for enrichment techniques. The Thomsen–Friedenreich (TF) antigen has been shown to be a tumor specific antigen in breast cancer. The aim of this study was to investigate the expression of TF on DTC-BM in 25 patients. Bone marrow samples were first double-stained by a Cy3 conjugated cytokeratin (CK) antibody (ab) A45 B/B3 (IgG) and anti-TF ab Nemod 2 (IgM), followed by Cy2 conjugated goat anti-mouse IgM ab. For further characterisation samples were also double-stained with anti-TF ab Nemod 2 (IgM), followed by Cy2 conjugated goat anti-mouse IgM ab, and anti MUC1 ab A76-A/C7 IgG, followed by Cy3 conjugated goat anti-mouse IgG. CK positive DTC-BM showed co-expression of TF antigen in 22/23 patients (96%) and 61 of 62 detected cells (98%). Mononuclear BM cells without CK expression were also negative for TF. All of the TF positive cells showed strong MUC1 expression. This is the first study showing co-expression of CK and TF as markers of DTC-BM. Double staining experiments of TF and MUC1 expression showed that MUC1 is the carrier protein of TF in these cells. As TF is a specific marker of DTC-BM, it could be used as a target for antibody based therapy and immunomagnetic enrichment techniques for the isolation of DTC-BM.

Keywords

Breast cancer Disseminated tumor cells Bone marrow Minimal residual disease Thomsen–Friedenreich antigen MUC1 Prognosis Metastasis Therapy