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Molecular and histopathological characterization of seminoma patients with highly elevated human chorionic gonadotropin levels in the serum

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Titel: Molecular and histopathological characterization of seminoma patients with highly elevated human chorionic gonadotropin levels in the serum
Autoren: Christoph Seidel, Finn-Ole Paulsen, Tim Nestler, Richard Cathomas, Marcus Hentrich, Pia Paffenholz, Carsten Bokemeyer, Axel Heidenreich, Daniel Nettersheim, Felix Bremmer
Weitere Verfasser: Seidel, Christoph, Paulsen, Finn-Ole, Nestler, Tim, Cathomas, Richard, Hentrich, Marcus, Paffenholz, Pia, Bokemeyer, Carsten, Heidenreich, Axel, Nettersheim, Daniel, Bremmer, Felix
Quelle: Virchows Arch
Verlagsinformationen: Springer Science and Business Media LLC, 2023.
Publikationsjahr: 2023
Schlagwörter: Male, Adult, Young Adult, Testicular Neoplasms, Biomarkers, Tumor, Humans, Original Article, Middle Aged, Seminoma, Adult [MeSH], Humans [MeSH], Middle Aged [MeSH], Immunohistochemistry [MeSH], Male [MeSH], Biomarkers, Tumor/blood [MeSH], Germ cell tumor, HCG, Testicular Neoplasms/blood [MeSH], Young Adult [MeSH], Seminoma/pathology [MeSH], Testicular Neoplasms/pathology [MeSH], Chorionic Gonadotropin/blood [MeSH], Biomarkers, Tumor/analysis [MeSH], Seminoma/blood [MeSH], Testicular cancer, Chorionic Gonadotropin, Immunohistochemistry, 3. Good health
Beschreibung: Approximately 30% of seminoma (SEM) patients present with moderately elevated human chorionic gonadotropin (hCG) levels at first diagnosis. In case of high hCG serum levels, the presence of a non-SEM component, i.e. choriocarcinoma (CC), may be assumed. To characterize cases described as pure seminoma with high serum hCG levels, tissue samples and DNA were analyzed. Patient files from an international registry were screened for patients with SEM and extraordinarily high hCG serum levels. IHC and qRT-PCR analysis was performed for markers of SEM, embryonal carcinoma (EC) and CC/trophoblast cells. The cell lines TCam-2 (SEM), 2102EP, NCCIT, NT2/D1 (EC) and JAR, JEG3 and BeWo (CC) were included for comparison. Of 1031 SEM patients screened, 39 patients (3.7%) showed hCG serum levels > 1000 U/l. Of these, tumor material for IHC and RNA for qRT-PCR was available from n = 7 patients and n = 3 patients, respectively. Median pre-orchiectomy serum hCG level was 5356 U/l (range: 1224–40909 U/L). Histopathologically, all investigated samples were classified as SEM with syncytiotrophoblast sub-populations. SEM cells were SALL4+ / OCT3/4+ / D2-40+, while syncytiotrophoblast cells were hCG+ / GATA3+ / p63+ and SOX2−/CDX2−. qRT-PCR analysis detected trophoblast stem cell markers CDX2, EOMES and TFAP2C as well as the trophectoderm-specifier TEAD4, but not GATA3. Additionally, SOX17 and PRAME, but not SOX2, were detected, confirming the pure SEM-like gene expression signature of the analyzed samples. In conclusion, excessively increased hCG serum levels can appear in patients with pure SEM. To explain detectable hCG serum levels, it is important to diagnose the subtype of a SEM with syncytiotrophoblasts.
Publikationsart: Article
Other literature type
Sprache: English
ISSN: 1432-2307
0945-6317
DOI: 10.1007/s00428-023-03698-0
Zugangs-URL: https://pubmed.ncbi.nlm.nih.gov/38097681
https://resolver.sub.uni-goettingen.de/purl?gro-2/139872
https://repository.publisso.de/resource/frl:6494476
Rights: CC BY
Dokumentencode: edsair.doi.dedup.....6f45c283362e88af868a1e000886b30e
Datenbank: OpenAIRE
Beschreibung
Abstract:Approximately 30% of seminoma (SEM) patients present with moderately elevated human chorionic gonadotropin (hCG) levels at first diagnosis. In case of high hCG serum levels, the presence of a non-SEM component, i.e. choriocarcinoma (CC), may be assumed. To characterize cases described as pure seminoma with high serum hCG levels, tissue samples and DNA were analyzed. Patient files from an international registry were screened for patients with SEM and extraordinarily high hCG serum levels. IHC and qRT-PCR analysis was performed for markers of SEM, embryonal carcinoma (EC) and CC/trophoblast cells. The cell lines TCam-2 (SEM), 2102EP, NCCIT, NT2/D1 (EC) and JAR, JEG3 and BeWo (CC) were included for comparison. Of 1031 SEM patients screened, 39 patients (3.7%) showed hCG serum levels > 1000 U/l. Of these, tumor material for IHC and RNA for qRT-PCR was available from n = 7 patients and n = 3 patients, respectively. Median pre-orchiectomy serum hCG level was 5356 U/l (range: 1224–40909 U/L). Histopathologically, all investigated samples were classified as SEM with syncytiotrophoblast sub-populations. SEM cells were SALL4+ / OCT3/4+ / D2-40+, while syncytiotrophoblast cells were hCG+ / GATA3+ / p63+ and SOX2−/CDX2−. qRT-PCR analysis detected trophoblast stem cell markers CDX2, EOMES and TFAP2C as well as the trophectoderm-specifier TEAD4, but not GATA3. Additionally, SOX17 and PRAME, but not SOX2, were detected, confirming the pure SEM-like gene expression signature of the analyzed samples. In conclusion, excessively increased hCG serum levels can appear in patients with pure SEM. To explain detectable hCG serum levels, it is important to diagnose the subtype of a SEM with syncytiotrophoblasts.
ISSN:14322307
09456317
DOI:10.1007/s00428-023-03698-0