title: Epidermal growth factor receptor expression and activation in nonseminomatous germ cell tumors.
abstract: OBJECTIVE
  The goal of this work was to study the expression of epidermal growth factor receptor (by use of monoclonal antibody EGFR 1) and HER-2/neu (by use of monoclonal antibody EGFR 2), as well as EGFR activation [phosphorylated EGFR (P-EGFR)] and autocrine stimulation [ligand transforming growth factor-alpha (TGF-alpha)] markers in a series of 24 testicular tumors [18 nonseminomatous germ cell tumors (GCTs), 1 Leydig cell tumor, and 5 seminomatous GCTs].
  
  
  METHODS
  Paraffin-embedded sections of tumors were studied immunohistochemically for beta-human chorionic gonadotropin (beta-HCG), EGFR 1, HER-2/neu, TGF-alpha, and P-EGFR expression. In one case of pure choriocarcinoma, fresh-frozen tumor sections were also evaluated. The presence of EGFR mRNA was studied in the Jar choriocarcinoma cell line using reverse transcription-PCR.
  
  
  RESULTS
  Staining for cell membrane EGFR was detected immunohistochemically in the 16 beta-HCG-positive components of 18 nonseminomatous GCTs as well as in the control Jar choriocarcinoma cell line and normal placenta. In contrast, 1 Leydig cell tumor, 5 seminomatous GCTs, and beta-HCG-negative components of 18 GCTs, as well as control B and T lymphoma cell lines, did not express EGFR. Expression of HER-2/neu, TGF-alpha, and P-EGFR was detected in 25, 36, and 27% of EGFR-positive, nonseminomatous GCTs, respectively. EGFR mRNA was detected in the Jar choriocarcinoma cells.
  
  
  CONCLUSIONS
  We report data, for the first time, that document EGFR and HER-2/neu expression and indicate EGFR activation and autocrine stimulation in beta-HCG-positive, nonseminomatous GCTs. These findings may be clinically relevant in relation to the recent availability of active EGFR- and HER-2/neu-targeted pharmaceutical agents and to the extensively described negative prognostic significance of beta-HCG expression in mixed GCTs.
authors.affiliation: The Falck Division of Medical Oncology, Department of Oncology and Hematology, Ospedale Niguarda Ca' Granda, I-20162 Milan, Italy. oncologia@ospedale-niguarda.it
authors.forename: M
authors.initials: M
authors.lastname: Moroni
authors.forename: S
authors.initials: S
authors.lastname: Veronese
authors.forename: R
authors.initials: R
authors.lastname: Schiavo
authors.forename: O
authors.initials: O
authors.lastname: Carminati
authors.forename: B S
authors.initials: BS
authors.lastname: Sorensen
authors.forename: M
authors.initials: M
authors.lastname: Gambacorta
authors.forename: S
authors.initials: S
authors.lastname: Siena
mesh_terms: D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000032:analysis; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D018237:Germinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016211:Transforming Growth Factor alpha / Q000032:analysis
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; D066246:ErbB Receptors; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha