Abstract B15: Unveiling the mechanism of ovarian cancer dissemination through a comparative study among primary tumors, ascites and metastases

Introduction & Objectives: Epithelial ovarian cancer (OC) is the most lethal gynecological malignancy and the fifth cause of cancer deaths in women in the western world. Largely asymptomatic, OC is frequently detected at late stage (75-80%). Five-year survival rate for women with advanced stage disease is less than 20%, while the cure rate is almost 90% when are diagnosed at early stages. Epithelial OC metastasizes by direct extension from the ovary seeding the cells into the peritoneal wall and to neighbouring organs. Our aim is to study the OC dissemination comparing human paired ovarian primary tumors, ascites and metastases. Material & Methods: Fresh ovarian primary tumor, ascites and peritoneal metastases from patients suffering advanced serous OC were collected at the surgery room and processed for further analysis. Formalin-fixed paraffin-embedded (FFPE) tissues were collected from the Pathology Department for further immunohistochemical analysis. Discovery phase: We determined the global gene expression profile of 5 fresh-paired samples (primary tumor, ascites and metastases) by microarray analysis. Validation phase: We analysed mRNA and protein levels from 10 unpaired fresh samples by RTqPCR and Western-blot, respectively. We further evaluated protein expression by immunohistochemistry from 10-paired tumor and metastasis FFPE-samples. Results: GREM1 was shown to be upregulated in metastases versus ascites and in metastases versus primary tumors. FABP4 and INHBA were significantly overexpressed in metastases when compared to primary tumors. INHBA and FABP4 were validated at RNA and protein level, whereas GREM1 only at RNA level. Conclusions: The present study highlights the role of previously unknown candidates in OC dissemination that might be used as tumor biomarkers, to clinically monitor the progression of the disease, or as target therapies, to block the OC dissemination. Citation Format: Lucia Lanau, Marina Rigau, Blanca Majem, Tatiana Altadill, Josep Castellví, José-Luis Sánchez-Iglesias, Assumpció Pérez-Benavente, Silvia Cabrera, Angel García, Jordi Xercavins, Josep-Maria Del Campo, Antonio Gil-Moreno, Anna Ruiz, Jaume Reventós, Marta Llauradó. Unveiling the mechanism of ovarian cancer dissemination through a comparative study among primary tumors, ascites and metastases. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): A