gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

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Expression Levels and Activation Status of Full-Length and Truncated Her2 Protein in Human Mammary Tumours May be a Positive Predictor For Her2-Directed Therapy Response

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  • corresponding author presenting/speaker Dirk Zielinski - Klinikum Kassel, Kassel, Deutschland
  • Josef Rüschoff - Klinikum Kassel, Kassel
  • Thomas Henkel - TARGOS Molecular Pathology GmbH, Kassel

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocOP471

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dkk2006/06dkk581.shtml

Published: March 20, 2006

© 2006 Zielinski et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Background: The humanized monoclonal antibodies Trastuzumab and, recently, Pertuzumab have been established for the treatment of Her-2-overexpressing metastatic breast cancers. Resistance to Her2-targeted therapy still remains a common phenomenon. Recent evidence shows that receptor activation status may be a predictor for Her-2 directed therapy response. In the herein presented study, biochemical features of the Her-2 molecule have been analysed by immunohistochemistry (IHC) and Western blot analysis.

Methods: Her-2 protein expression status in FFPE tissue was determined using DAKO HercepTest and scoring system. Her-2 phosphorylation was analysed by IHC in cases scored 2+ or 3+ by DAKO scoring. Whole tissue lysates of corresponding fresh frozen tissue samples were prepared and analysed for the same parameters by Western blot.

Results: Tissue specimens from 34 patients and the Herceptin-sensitive SkBr3-cell line were analysed. By means of IHC, Her-2 Tyr1248 phosphorylation was detected in 16 (50%) of Her-2 positive cases. Western blot analysis revealed Her-2p95 expression in almost equal amounts in every patient, whereas expression levels of Her-2 full length protein varied greatly. Phosphorylation of the full-length Her-2p185 molecule was detected in only 10 (31%) cases, including the SkBr3 cell line.

Conclusion: These preliminary results suggest that presence of phosphorylated Her-2p185 protein may be a predictor of Her-2 targeted therapy response. The diagnostic relevance of these findings will be evaluated in a subsequent study where samples from patients with known clinical follow-up data will be analysed.