Abstract 448: Expression of Galectins in high grade serous ovarian cancer

Abstract

Abstract Ovarian cancer (OC) is the 5th leading cause of cancer-related deaths in the Western world. Despite improvements in various treatments, the five-year survival of patients with advanced stage disease remains less than 40%. Approximately 70% of malignant OCs are attributed to the high-grade serous carcinoma (HGSC) histological subtype, which is typically treated by a surgical tumor debulking followed by platinum/taxane chemotherapy. Unfortunately, although approximately 80% of patients respond well to the initial chemotherapy treatment, a large portion of patients develop drug resistance during subsequent cycles of chemotherapy. The non-uniformity of response to therapy complicates the clinical decision-making process and reflects the genetic complexity that gives rise to intra-tumor heterogeneity. Clearly, there is an urgent need to develop reliable clinical biomarkers to identify patients at different levels of risk for specific outcomes. Here, we have investigated the expression of galectins (gal) in HGSC and examined their potential as biomarkers. Galectins have been shown to play a dual role in cancer progression. When released in the extracellular space by cancer cells, they are particularly efficient in creating an immunosuppressive tumor microenvironment, both locally and systemically. Inside cancer cells, they provide cancer cells with increased resistance to apoptosis induced by chemotherapeutic agents. Using tissue microarrays constructed from formalin fixed paraffin embedded tissues from 209 patients with HGSC, we have identified a new protein signature that takes into account the expression of galectins in both cancer and stromal cells. Our study showed that increased protein expression of stromal gal-1 and epithelial gal-8/9 in primary tumors was associated with a poor response to treatment in patients with HGSC. This signature also increased the predictive value of CA-125 on five-year disease-free survival, chemotherapy treatment response and five-year overall survival. Univariate and multivariate analyses revealed that gal-8 and gal-9 were both independent predictors of chemoresistance and overall survival, respectively. From a fundamental point of view, our project also contributes to better define the heterogeneity of the disease. Overall, these data provide a rational for further studies of Galectins in OC. Citation Format: Marilyne Labrie, Laudine Communal, Maria-Claudia Vladoiu, Pascal Dupont, Anne-Marie Mes-Masson, Yves St-Pierre. Expression of Galectins in high grade serous ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 448.