Abstract B26: Cell surface expression of CD44v8-10 is associated with good prognosis while cleaved extracellular domain is a marker of poor prognosis in high-grade serous epithelial ovarian cancer.
Authors: Pepin David , Sosulski Amanda , Horn Heiko , Zhang Lihua , Coletti Caroline , Vathipadiekal vinod , Castro Cesar M. , Birrer Michael J. , Nagano Osamu , Saya Hidekuyi , Lage Kasper , Donahoe Patricia K. 
Published: May 2016

CD44 is a transmembrane hyaluronic acid receptor gene that encodes over 100 different tissue specific protein isoforms. The most prevalent, standard CD44 (CD44s), has been used as one of a panel of markers identifying a stem cell enriched population in ovarian cancer. While expression of the CD44 epithelial specific variant containing exons v810 (CD44v810) has been associated with more resistant and metastatic tumors in gastrointestinal and breast cancers, its role in highgrade serous ovarian cancer is unknown. The gene expression profiles from a cohort of 254 tumor samples, of The Cancer Genome Atlas RNAseqV2 ovarian serous cystadenocarcinoma collection, were analyzed for expression of different CD44 isoforms. A trend for longer survival was observed in patients with tumors with high expression of CD44 isoforms that include exons V8-10. Immunohistochemical analysis of tumors using an antibody recognizing CD44v810 (rat antiCD44v9 RV3) was performed on an independent cohort of 210 patients with high-grade serous ovarian cancer using a tumor tissue microarray. Patient stratification based on unbiased software analysis of staining revealed a statistically significant increase in survival in patients with the highest levels of protein expression compared to those with the lowest expression with a median survival time in the top 10% of 1203 days versus 751 days for the bottom 10% (p= 0.001). Immunohistochemical expression of CD44v810 transmembrane protein in primary ovarian cancer cell lines was correlated with a predominantly epithelial phenotype characterized by high expression of epithelial markers and low expression of mesenchymal markers by principal component analysis. Conversely, detection of proteolytically cleaved and secreted extracellular domain of CD44v810 (solCD44v810) in patient ascites samples was correlated with significantly worse prognosis. Therefore, presence of transmembrane CD44v8-10 on the surface of primary tumor cells may be a marker of a highly epithelial tumor with better prognosis while enzymatic cleavage of CD44v8-10, as detected by presence of the soluble extracellular domain in ascites fluid, may be indicative of a more metastatic disease with worse prognosis.

Citation Format: David Pepin, Amanda Sosulski, Heiko Horn, Lihua Zhang, Caroline Coletti, vinod Vathipadiekal, Cesar M. Castro, Michael J. Birrer, Osamu Nagano, Hidekuyi Saya, Kasper Lage, Patricia K. Donahoe. Cell surface expression of CD44v8-10 is associated with good prognosis while cleaved extracellular domain is a marker of poor prognosis in high-grade serous epithelial ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B26.