title: Ezrin promotes ovarian carcinoma cell invasion and its retained expression predicts poor prognosis in ovarian carcinoma.
abstract: The majority of patients diagnosed with ovarian carcinoma are classified as being in advanced stage of disease. In a situation of cancer spread throughout the abdominal cavity, a successful curative treatment is difficult to achieve. Therefore, preventing binding of tumor cells to the mesothelium is crucial for patients' outcome. One important mechanism is the interaction between hyaluronic acid and the CD44 receptor with its submembrane linking complex. This consists of ezrin, radixin, and moesin and connects the CD44 receptor with the cytoskeleton. To assess the role of ezrin and moesinfor ovarian carcinoma progression, we analyzed ovarian carcinoma samples from 105 patients for expression of ezrin and moesin by immunohistochemistry and correlated these data with several clinicopathological parameters. To elucidate the functional importance of ezrin and moesin, their expression was inhibited in SKOV-3 cells by RNA interference. Ezrin and moesin were strongly expressed in 49 and 48% of ovarian carcinoma samples, respectively, and their presence correlated with reduced overall survival in univariate analysis (ezrin, p=0.0189; moesin, p=0.0351). In multivariate analysis (including FIGO stage, residual tumor, histological type, and Silverberg grading), ezrin still remained significant as an independent risk factor (relative risk, 2.39; p=0.012). In SKOV-3 cells, siRNA against ezrin but not moesin inhibited in vitro invasion. These data imply that ezrin is necessary for tumor cell invasion, and the better prognosis of ovarian carcinomas lacking ezrin is probably related to their impaired invasion.
authors.affiliation: Department of Pathology, Martin Luther University Halle-Wittenberg, and Department of Gynecology, St. Elisabeth Hospital, Halle, Germany. martin.koebel@medizin.uni-halle.de
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
authors.forename: Elise
authors.initials: E
authors.lastname: Gradhand
authors.forename: Katharina
authors.initials: K
authors.lastname: Zeng
authors.forename: Wolfgang D
authors.initials: WD
authors.lastname: Schmitt
authors.forename: Karen
authors.initials: K
authors.lastname: Kriese
authors.forename: Tilmann
authors.initials: T
authors.lastname: Lantzsch
authors.forename: Matthias
authors.initials: M
authors.lastname: Wolters
authors.forename: Jürgen
authors.initials: J
authors.lastname: Dittmer
authors.forename: Hans G
authors.initials: HG
authors.lastname: Strauss
authors.forename: Christoph
authors.initials: C
authors.lastname: Thomssen
authors.forename: Steffen
authors.initials: S
authors.lastname: Hauptmann
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012307:Risk Factors; D016019:Survival Analysis; D014162:Transfection; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D000099149:Ezrin; C071058:moesin