title: The clinical role of epithelial-mesenchymal transition and stem cell markers in advanced-stage ovarian serous carcinoma effusions.
abstract: We recently identified gene signatures that allow classification of ovarian carcinoma into 5 distinct clinically relevant groups. In the present study, we investigated the clinical role of 10 protein products of the discriminating genes, with focus on epithelial-mesenchymal transition and stem cell markers. Expression of E-cadherin, N-cadherin, P-cadherin, Zeb1, HMGA2, Rab25, CD24, NCAM (CD56), Sox11, and vimentin was assessed in 100 advanced-stage (International Federation of Gynecology and Obstetrics stages III-IV) serous ovarian carcinoma effusions using immunohistochemistry. Results were analyzed for association with clinicopathological parameters, including chemotherapy response, and survival. All 10 proteins were frequently expressed in carcinoma cells. HMGA2 expression was related to older age (P = .015). HMGA2 and NCAM expression was related to stage III disease (P = .011 and P = .023, respectively), and NCAM was overexpressed in peritoneal compared with pleural effusions (P = .001). Vimentin and Zeb1 expression was significantly related to poor chemotherapy response at diagnosis (P = .005 and P = .017, respectively). The associations between NCAM and peritoneal localization and of vimentin and poor chemoresponse were retained after Bonferroni correction. NCAM expression was associated with a trend for shorter overall survival in univariate survival analysis (P = .187), but emerged as an independent prognosticator in Cox multivariate analysis (P = .042). This study identifies vimentin and Zeb1 as markers of poor chemoresponse in metastatic serous ovarian carcinoma effusions and suggests NCAM as potential prognostic marker in metastatic disease. The generally limited prognostic role of the studied markers emphasizes the difficulty in applying data obtained in studies of primary ovarian carcinomas to analyses of ovarian carcinoma effusions, reflecting the unique biology of the latter.
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0424 Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, N-0424 Oslo, Norway. Electronic address: bend@medisin.uio.no.
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0424 Oslo, Norway.
authors.forename: Arild
authors.initials: A
authors.lastname: Holth
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0424 Oslo, Norway.
authors.forename: Ellen
authors.initials: E
authors.lastname: Hellesylt
authors.affiliation: Cancer Science Institute (CSI), Yong Loo Lin School of Medicine, National University of Singapore, MD6 Centre for Translational Medicine, 117599 Singapore.
authors.forename: Tuan Zea
authors.initials: TZ
authors.lastname: Tan
authors.affiliation: Cancer Science Institute (CSI), Yong Loo Lin School of Medicine, National University of Singapore, MD6 Centre for Translational Medicine, 117599 Singapore; Department of Obstetrics and Gynaecology, National University Health System, 1E Kent Ridge Road, 119228 Singapore.
authors.forename: Ruby Yun-Ju
authors.initials: RY
authors.lastname: Huang
authors.affiliation: Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, N-0424 Oslo, Norway; Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, N-0424 Oslo, Norway.
authors.forename: Claes
authors.initials: C
authors.lastname: Tropé
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0424 Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, N-0424 Oslo, Norway.
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.affiliation: Cancer Science Institute (CSI), Yong Loo Lin School of Medicine, National University of Singapore, MD6 Centre for Translational Medicine, 117599 Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, MD6 Centre for Translational Medicine, 117599 Singapore; Institute of Molecular and Cell Biology (IMCB) A*STAR, Proteos 138673, Singapore.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Thiery
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D016009:Chi-Square Distribution; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000737:chemistry* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000737:chemistry* / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000032:analysis; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D019007:P-Selectin / Q000032:analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis; D016896:Treatment Outcome; D014746:Vimentin / Q000032:analysis; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D019006:Neural Cell Adhesion Molecules; D019007:P-Selectin; C546937:SELP protein, human; D014157:Transcription Factors; D014746:Vimentin; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1
keywords: Chemoresistance; Effusion; Epithelial-mesenchymal transition; Ovarian carcinoma; Survival