276P - Overexpression of HER3 and the survival of ovarian cancer

Abstract

Background: Human epidermal growth factor receptor-2 (HER2) and 3 (HER3) belongs to epidermal growth factor receptor (EGFR) family of transmembrane receptor tyrosine kinases which is responsible for cell survival and proliferation, but their role in ovarian cancer is not yet established. In this study, their status in specimens of epithelial ovarian cancer was determined with immunohistochemistry (IHC) and in situ hybridization (ISH) and was analyzed to find out the correlation with clinical features of ovarian cancer. Methods: Tissue microarrays (TMAs) were prepared from paraffin blocks of 105 ovarian tumor samples. The immunohistochemical expression of HER2, HER3, PI3K, Akt, p-Akt, mTOR, p-mTOR, S6 and p-S6 were investigated. HER2 and HER3 gene amplifications were evaluated by ISH. The correlation between status of materials and disease outcome of the patients were analyzed. Results: HER2 positivity was 3.8% on IHC and 5.7% on ISH, otherwise HER3 showed 12.4% and 8.6% expression respectively. The concordances of IHC and ISH were 98.1% (103/105) in HER2, and 82.9% (87/105) in HER3. HER2 status was not related with disease outcome of ovarian cancer. However, the HER3 status on FISH was associated with rapid disease progression, and this was a significant risk factor even after adjusting other possible risk factors in multivariate analysis. Conclusions: HER3 could be an independent marker for poor prognosis in ovarian cancer, because HER3 signaling pathway might be distinguished from that of HER2. The possibility of target therapy in patients with HER3 gene alteration should be evaluated in the field of ovarian cancer. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.