Epithelial ovarian cancer is a highly metastatic disease and the leading cause of death among
cancer of the female genital tract. Abnormal
epidermal growth factor receptor (EGFR) signalling has been shown to be involved in epithelial-mesenchymal transition (EMT), an early step during
metastasis. Additionally, over-expression of the
E-cadherin repressor Snail, a key regulator of EMT, has previously been found to be associated with unfavourable prognostic features. Thus, the aim of our study was to elucidate the role of EGFR-dependent signalling pathways for Snail expression in
ovarian cancer. For this purpose, we analysed 25
formalin-fixed and
paraffin-embedded (FFPE) primary tumours and their corresponding
metastases for the expression of 25 signalling pathway molecules by reverse phase
protein arrays. We found a significant correlation of Snail with EGFR((Tyr1086)) and
p38 MAPK((Thr180/Tyr182)) in primary ovarian
carcinoma and with EGFR((Tyr1086)) in their corresponding
metastasis. Additionally, we showed that high expression levels of Snail in primary tumours combined with high expression levels of the phosphorylated
p38 MAPK((Thr180/Tyr182)) in
metastasis lead to an increased risk for death in ovarian
carcinoma patients. Thus, for future combinatorial
cancer therapy, drug combinations that best target the deregulated
protein network in each individual patient should be selected.