Epidermal growth factor receptor expression and activation in nonseminomatous germ cell tumors.
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.
Moroni
M
M
The Falck Division of Medical Oncology, Department of Oncology and Hematology, Ospedale Niguarda Ca' Granda, I-20162 Milan, Italy. oncologia@ospedale-niguarda.it
Veronese
S
S
Schiavo
R
R
Carminati
O
O
Sorensen
B S
BS
Gambacorta
M
M
Siena
S
S
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
D018997:Chorionic Gonadotropin, beta Subunit, Human; D066246:ErbB Receptors; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha