Rare expression of target antigens for immunotherapy on disseminated tumor cells in breast cancer patients without overt metastases

  • Authors:
    • Sabine Kasimir-Bauer
    • Friedrich Otterbach
    • Carsten Oberhoff
    • Kurt Werner Schmid
    • Rainer Kimmig
    • Siegfried Seeber
  • View Affiliations

  • Published online on: December 1, 2003     https://doi.org/10.3892/ijmm.12.6.969
  • Pages: 969-975
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Abstract

Occult disseminated tumor cells are the major cause of relapse in patients with primary operable breast cancer but detection and characterization of these few cells is difficult. Applying immunohistochemistry, an immunomagnetic enrichment technique (IET) and immunocytochemistry (IC), we studied 58 breast cancer patients without overt metastases for the frequency of cytokeratin-positive (CK+) bone marrow (BM) cells coexpressing the epithelial adhesion molecule 17-1A (EpCAM) and c-erbB-2 and analyzed the primary tumor for these antigens as a strategy for additional immunotherapy. The primary tumors were analyzed for the target antigens by a pathologist. Dissemination of CK+ cells was studied in 4-6x106 BM cells by IC alone. For characterization of CK+ cells, 10-15x106 BM cells were incubated with microbeads coupled to antibodies detecting the target antigens, labelled cells were separated on selection columns and the positively (BM cells carrying the target antigen) and negatively (BM cells without target antigen) selected fractions were stained for CK+ cells. The effectiveness of these methods was confirmed in cell culture models. 17-1A was detected in all primary tumors and c-erbB-2 overexpression (2+, 3+) was found in 25/58 tissue samples. In total, analyzing 15-20x106 BM cells in each patient, the detection rate for CK+ cells in the BM was 69% (40/58 patients). Interestingly, analysis of the positive and negative enrichment fractions showed that the 17-1A antigen was coexpressed on CK+ cells in only 6 patients and c-erbB-2/CK+ cells were found in only one patient. Although 17-1A and c-erbB-2 were frequently detected in the primary tumor, these antigens were rarely expressed on CK+ BM cells. Whether the applied IET is not able to detect low amounts of these target antigens has to be clarified. Nevertheless, applying cell-cycle independent protocols in clinical trials requires careful elucidation of those patients who might benefit from these therapies.

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December 2003
Volume 12 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kasimir-Bauer S, Otterbach F, Oberhoff C, Schmid KW, Kimmig R and Seeber S: Rare expression of target antigens for immunotherapy on disseminated tumor cells in breast cancer patients without overt metastases. Int J Mol Med 12: 969-975, 2003
APA
Kasimir-Bauer, S., Otterbach, F., Oberhoff, C., Schmid, K.W., Kimmig, R., & Seeber, S. (2003). Rare expression of target antigens for immunotherapy on disseminated tumor cells in breast cancer patients without overt metastases. International Journal of Molecular Medicine, 12, 969-975. https://doi.org/10.3892/ijmm.12.6.969
MLA
Kasimir-Bauer, S., Otterbach, F., Oberhoff, C., Schmid, K. W., Kimmig, R., Seeber, S."Rare expression of target antigens for immunotherapy on disseminated tumor cells in breast cancer patients without overt metastases". International Journal of Molecular Medicine 12.6 (2003): 969-975.
Chicago
Kasimir-Bauer, S., Otterbach, F., Oberhoff, C., Schmid, K. W., Kimmig, R., Seeber, S."Rare expression of target antigens for immunotherapy on disseminated tumor cells in breast cancer patients without overt metastases". International Journal of Molecular Medicine 12, no. 6 (2003): 969-975. https://doi.org/10.3892/ijmm.12.6.969