Analysis of expression of Eph/Ephrin tyrosine kinases in advanced ovarian cancer

Abstract

5105 Background: Eph-receptor protein tyrosine kinases and their ligands (Ephrins) play important roles in embryological development including axonal migration and angiogenesis. They are over expressed in many cancers. Aim of our study was to examine the patterns of expression of this receptor family and their impact on outcome in advanced ovarian cancer. Methods: Eph A1, Eph A2, Ephrin A1, Ephrin A5, Eph B2, Eph B3, Eph B6 and Ephrin B1 mRNA expression was examined by real time quantitative PCR on 25 ovarian cancer specimens, two normal ovarian tissue, two benign ovarian tumours, two cancer cell lines and one normal ovarian epithelial cell line. Progression free survival (PFS) was calculated by retrospective review of medical records. Results: 25 specimens were obtained after debulking surgery for stage III /IV ovarian cancer. Adjuvant platinum based chemotherapy was given to all patients. Median PFS was 14 months (3–33 months). All receptors and ligands studied except Ephrin B1 were minimally expressed in normal and benign specimens whereas their expression was more than five fold in one third of the cancer specimens. Eph A1 and Eph A2 expression was significantly correlated with the expression of their ligand Ephrin A1 (r=0.506; p= 0.007 and r=0.466; p=0.014 respectively). Similar correlation was found between expression of Eph B2 and Eph B3 and their ligand Ephrin B1(r=0.452; p=0.018 and r=0.577; p= 0.002 respectively). Expression of Ephrin A5 was associated with shorter PFS (r= - 0.465; p = 0.022). Conclusions: Ephs and Ephrins are over expressed in ovarian carcinoma and Ephrin A5 predicted shorter PFS. Co-expression of receptors and their ligands in the same specimen suggests that this is an active system and may have a role in tumour progression or metastasis. If these results are confirmed, they could be used as targets for biological therapies. No significant financial relationships to disclose.