title: EPCAM-A novel molecular target for the treatment of pediatric and adult germ cell tumors.
abstract: Germ cell tumors (GCTs) are thought to develop from totipotent primordial germ cells. Although the epithelial cell adhesion molecule (EPCAM) is expressed on embryonic stem cells as well as different tumor cells, it has not yet been extensively studied in GCTs. We analyzed EPCAM expression by quantitative RT-PCR in 48 fresh-frozen GCT specimens of different histology (10 mature teratoma, MT; 6 immature teratoma, IT; 7 dysgerminoma; 6 mixed malignant GCTs; 19 yolk sac tumor, YST) and in the GCT cell lines NCCIT, TE76.T, JAR and 2102Ep, and correlated its expression with AFP and hCG protein levels, histologic differentiation, and clinical follow-up data. EPCAM protein was visualized by immunohistochemistry of selected corresponding paraffin embedded tumor tissues. EPCAM was expressed in malignant but not in benign GCTs irrespective of age, sex, site and clinical stage of tumor (P = 0.001). In primary teratomas, EPCAM expression increased with their grade of immaturity (mean 2(-ΔCt) values: MT 0.23, IT 1.61, P = 0.007) and significantly correlated with serum AFP (P = 0.03) and hCG (P = 0.03) levels in malignant GCTs. Particularly high EPCAM levels were found in nonseminomatous GCTs such as YSTs (8.49) and choriocarcinoma (13.54). Immunohistochemical analysis verified gene expression data showing a distinct EPCAM staining in YST. Similarly in vitro, highest EPCAM expression was measured in GCT cell lines comprising yolk sac (2102Ep: 5.59) or choriocarcinoma (JAR: 10.65) components. This first comprehensive analysis of EPCAM in GCTs revealed high EPCAM expression in YSTs and choriocarcinomas. Thus, these nonseminomatous GCTs may be interesting targets for EPCAM immunotherapy, which has to be evaluated in further studies.
authors.affiliation: Department of Pediatric Hematology and Oncology, University of Bonn, University Children's Hospital Bonn, Germany. stefan.schoenberger@ukb.uni-bonn.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Schönberger
authors.forename: Vera
authors.initials: V
authors.lastname: Okpanyi
authors.forename: Gabriele
authors.initials: G
authors.lastname: Calaminus
authors.forename: Sebastian
authors.initials: S
authors.lastname: Heikaus
authors.forename: Ivo
authors.initials: I
authors.lastname: Leuschner
authors.forename: James C
authors.initials: JC
authors.lastname: Nicholson
authors.forename: Nikolas H
authors.initials: NH
authors.lastname: Stoecklein
authors.forename: Dominik T
authors.initials: DT
authors.lastname: Schneider
authors.forename: Arndt
authors.initials: A
authors.lastname: Borkhardt
mesh_terms: D000293:Adolescent; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D012333:RNA, Messenger