gms | German Medical Science

Aims: Overexpression of the receptor tyrosine kinase Her-2 in mammary tumours was shown to correlate with worse prognosis. The humanized monoclonal antibody Trastuzumab (Herceptin) has become the most important drug for the treatment of such cancers, although resistance to Her2-targeted therapy still remains a common phenomenon. Recent evidence shows that changes in the Her-2 associated signal transduction pathways may help to predict therapy response.

Methods: 120 randomly chosen cases of FFPE tissue of primary breast tumours were screened for expression and activation of selected marker proteins by means of IHC. These proteins represent the Her-2 associated and -induced signal transduction from growth factors and their receptors to signal transduction intermediates and transcription factors. Matrix metalloproteases and their inhibitors (TIMPs) were also considered as possible sensor proteins. The activation status of many of the investigated proteins was determined by using phospho-specific antibodies.

Results: The applied method revealed a detailed insight into signal transduction in mammary tumours. Expression level and activation state of some of the investigated proteins correlated well with clinical and histopathological parameters.

Conclusion: Changes in signal transduction may contribute to Her-2 directed therapy resistance. However, the diagnostic relevance of the thus far analysed possible markers will be evaluated in a subsequent study where samples from patients with known therapy outcome data.