title: VICKZ2 protein expression in ovarian serous carcinoma effusions is associated with poor survival.
abstract: The involvement of VICKZ proteins has been implicated in a large number of cancers. The aim of the present study was to investigate the biological and clinical role of VICKZ proteins in ovarian carcinoma (OC). VICKZ1-3 protein expression was analyzed in 82 serous OC specimens (51 effusions, 14 primary carcinomas, 17 solid metastases) by immunoblotting. Protein localization was studied using immunohistochemistry in 101 tumors (40 effusions, 25 primary carcinomas, 36 solid metastases). The effect of VICKZ silencing using short hairpin RNA on collagenolytic activity and invasion was assessed in ES-2 OC cells. VICKZ2 was the most frequently expressed family member in serous carcinomas. VICKZ levels measured by pan-VICKZ antibody were significantly higher in primary carcinomas and solid metastases compared to effusions (P < .001). In contrast, VICKZ1 and VICKZ2 were overexpressed in effusions compared to primary carcinomas and solid metastases (P = .016 and P = .024, respectively), and higher VICKZ2 expression in effusions was associated with shorter overall survival in univariate analysis (P = .01). All 3 proteins were localized to OC cells by immunohistochemistry, with tumor-specific expression observed for VICKZ1 and VICKZ2. VICKZ silencing in ES-2 cells led to reduced matrix metalloproteinase 9 activity and reduced invasion. In conclusion, VICKZ2 is the most frequently expressed VICKZ family member in serous OCs. VICKZ1 and VICKZ2 are overexpressed in effusions compared to primary carcinomas and solid metastases, suggesting a biological role at this anatomical site, and appear to have a role in proteolysis and invasion. VICKZ2 may be a prognostic marker in ovarian serous carcinoma effusions.
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway; University of Oslo, Faculty of Medicine, Institute of Clinical Medicine, N-0310 Oslo, Norway. Electronic address: bend@medisin.uio.no.
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Yifat B Z
authors.initials: YB
authors.lastname: Rosenfeld
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
authors.forename: Arild
authors.initials: A
authors.lastname: Holth
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
authors.forename: Ellen
authors.initials: E
authors.lastname: Hellesylt
authors.affiliation: University of Oslo, Faculty of Medicine, Institute of Clinical Medicine, N-0310 Oslo, Norway; Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
authors.forename: Claes G
authors.initials: CG
authors.lastname: Tropé
authors.affiliation: Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Reuven
authors.initials: R
authors.lastname: Reich
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Joel K
authors.initials: JK
authors.lastname: Yisraeli
mesh_terms: D000328:Adult; D000368:Aged; D001202:Ascitic Fluid / Q000378:metabolism* / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015996:Survival Rate
chemical_list: C406144:IGF2BP1 protein, human; D016601:RNA-Binding Proteins
keywords: Effusions; Ovarian carcinoma; Survival; Tumor progression; VICKZ