gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

Her2/neu expression on disseminated tumor cells in the bone marrow and on the primary tumor – an insight into tumor biology

Meeting Abstract

  • corresponding author presenting/speaker Brigitte Rack - Frauenklinik der LMU, Klinikum Innenstadt, München, Deutschland
  • Alexandra Schoberth - Labor Drs. Tiller und Partner, München
  • Christian Schindlbeck - Frauenklinik der LMU, Klinikum Innenstadt, München
  • Sandra Schulze - Frauenklinik der LMU, Klinikum Innenstadt, München
  • Wolfgang Janni - Frauenklinik der LMU, Klinikum Innenstadt, München
  • Maja Heinrigs - Frauenklinik der LMU, Klinikum Innenstadt, München
  • Eva-Maria Genss - Frauenklinik der LMU, Klinikum Innenstadt, München
  • Barbara Strobl - Frauenklinik der LMU, Klinikum Innenstadt, München
  • Thomas Blankenstein - Frauenklinik der LMU, Klinikum Innenstadt, München
  • Udo Jeschke - Frauenklinik der LMU, Klinikum Innenstadt, München
  • Harald Sommer - Frauenklinik der LMU, Klinikum Innenstadt, München
  • Klaus Friese - Frauenklinik der LMU, Klinikum Innenstadt, München

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocOP054

The electronic version of this article is the complete one and can be found online at:

Published: March 20, 2006

© 2006 Rack et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Background: While the prognostic impact of disseminated tumor cells in bone marrow (DTC) at primary diagnosis of breast cancer has reached LOE I (Braun et al., NEJM 2005), there is also growing evidence that the presence of DTC during follow-up indicates an increased risk for subsequent recurrence (Janni, Cancer 2005). Therefore, DTC might proof as potential target for tailored treatment options in these patients. Aim of this study was to establish a new method to analyse cytokeratin-positive (CK+) cells for her2/neu gene amplification.

Methods: DTC were detected using a standardized immunoassay with monoclonal antibody A45-B/B3, directed against cytokeratin 8,18,19 (CK) and stained according to the APAAP-technique. 2 x 106 cells per patient were screened by bright field microscopy. Subsequently, cytospins with CK-positive cells were further characterized by fluorescence in situ hybridisation (FISH) using a her2/neu DNA probe (Zymed, Germany) or a multi-colour probe (Vysis,Il., USA) for hybridisation of centromer 17 (polyploidy) and the her2/neu growth factor gene. A ratio of her2/neu and centromer chr. 17 signals of at least two was regarded as amplification.

Results: 232 bone marrow aspirates of 156 patients with breast cancer were analyzed at the time of primary diagnosis and during follow-up. DTC were detected in 68 samples (29%) in this patient group. The median number of detected cells was 2 (range 1 – 58). In 45 randomly assigned aspirates with DTC, the her2/neu status on these cells was evaluated and 13 samples were diagnosed with her2/neu amplification on DTC (29%). In 41 cases, both the her2/neu status of the primary tumor and on CK+ cells was available. In comparison, in 31 cases (76%) her2/neu status on the primary tumor corresponded to the her2/neu status on DTC. 7 patients (17%), however, with her2/neu overexpression or amplification on the primary tumor showed her2/neu negative DTC, whereas in 3 patients (7%) with her2/neu negative tumors we found DTC with her2/neu amplification.

Conclusion: In a relevant subgroup of patients, heterogeneity of antigen expression results in a discrepancy of her2/neu status between the primary tumor and DTC in the bone marrow. Therefore, the amplification of her2/neu on persisting DTC may proof useful to stratify patients for tailored treatment strategies. Ongoing clinical trials are evaluating the effect of trastuzumab in these patients.

Figure1 [Fig. 1]