transforming-growth-factor-alpha and Testicular-Neoplasms

Molecular genetic alterations of known protoncogenes and growth factors, e.g. c-kit and its ligand SCF as well as hst1 and c-myc, are likely to play a role in the development of testicular cancer. In addition, identification and analysis of genes located on the frequently altered chromosome 12 represent an important focus of research. Genetic alterations may occur in a stepwise fashion, as described in other human tumors, leading to the development of the various histologic subtypes of testicular germ cell tumors. The characterization of these alterations are most likely to extend the traditional histopathologic tumor classifications.

Topics: Biomarkers, Tumor; Chromosome Aberrations; Chromosomes, Human, Pair 12; Embryonal Carcinoma Stem Cells; ErbB Receptors; Fibroblast Growth Factor 3; Fibroblast Growth Factor 4; Fibroblast Growth Factors; Gene Amplification; Gene Expression Regulation, Neoplastic; Genetic Markers; Germinoma; Humans; Male; Molecular Biology; Neoplastic Stem Cells; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-kit; Proto-Oncogene Proteins c-myc; Proto-Oncogenes; Receptor Protein-Tyrosine Kinases; Receptor, ErbB-2; Receptors, Colony-Stimulating Factor; RNA, Messenger; Testicular Neoplasms; Transforming Growth Factor alpha

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].. 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.. 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.. 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.

Topics: Chorionic Gonadotropin, beta Subunit, Human; ErbB Receptors; Gene Expression Regulation, Neoplastic; Germinoma; Humans; Immunohistochemistry; Male; Phosphorylation; Receptor, ErbB-2; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Testicular Neoplasms; Transforming Growth Factor alpha

We analyzed expression of transforming growth factor (TGF)-alpha, epidermal growth factor (EGF) and their receptor, EGF receptor (EGFR), by immunohistochemistry in the human testis to determine the possible roles of these growth factors in human testicular function. Specimens were obtained from 17 patients including 9 patients with infertility, 4 patients with prostatic carcinoma and 4 patients with contralateral testicular tumor. EGF immunoreactivity was positive in the hyperplasic Leydig cells of one patient but negative in the other cases. On the other hand, strong TGF-alpha immunoreactivity was observed in Leydig cells, with weak staining in Sertoli cells and germ cells in cases with normal spermatogenesis. EGFR immunoreactivity was observed in the Leydig and peritubular cells, appearing as membrane staining. Marked immunoreactivity for TGF-alpha was observed in the Sertoli cells in testes with decreased spermatogenesis, especially in the Sertoli-cell-only syndrome. This finding may indicate a compensatory increase of TGF-alpha expression in the Sertoli cells accompanying a decrease in spermatogenesis. No significant correlation was found between the degrees of spermatogenesis and immunolocalization of the EGF receptor. These findings suggest that TGF-alpha is a locally produced growth factor that is involved in spermatogenesis in the human testis via an autocrine and/or paracrine mechanism.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Epidermal Growth Factor; ErbB Receptors; Humans; Immunohistochemistry; Infertility, Male; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms; Spermatogenesis; Testicular Neoplasms; Testis; Transforming Growth Factor alpha