Histopathological and molecular features of late relapses in non-seminomas

Frank Mayer, Hendrik Wermann, Peter Albers, Hans Stoop, Ad J M Gillis, Jörg T Hartmann, C Carsten Bokemeyer, J Wolter Oosterhuis, Leendert H J Looijenga, Friedemann Honecker

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

25 Citaten (Scopus)


OBJECTIVE: • To describe the histopathological types of late relapses of germ cell tumours and to search for molecular markers associated with chemotherapy resistance.

PATIENTS AND METHODS: • Samples from 14 patients with late relapse from a non-seminoma were analysed. • Archival tumour tissue was gathered at intial diagnosis (n= 9) and at relapse (n= 9), mostly after previous treatment with chemotherapy. • In addition to routine histopathology, tumours were analysed for microsatellite instability and screened for mutations in the KRAS and BRAF genes.

RESULTS: • Relapse occurred after 76.5 months (median, range: 24-209 months). • The histology in relapse was pure yolk sac tumour in four of the nine patients analysed. • Three had a non-germ cell malignancy, one was a mixed non-seminoma and one was a pure mature teratoma. • One sample with non-germ cell malignancy originated from a yolk sac tumour without any evidence of teratoma. • In four of 12 evaluable patients, high-level microsatellite instability was observed. • All patients were KRAS wild-type but four showed a BRAF mutation at V600E.

CONCLUSIONS: • Many late relapses of germ cell tumours show pure yolk sac histology. • Non-germ cell malignancies do not necessarily develop from teratoma but can also arise from yolk sac histology. • The biology underlying chemotherapy resistance in late relapse could be related to a high incidence of microsatellite instability and BRAF mutation V600E, which were found in half of the patients.

Originele taal-2Engels
Pagina's (van-tot)936-43
Aantal pagina's8
TijdschriftBJU international
Nummer van het tijdschrift6
StatusGepubliceerd - mrt. 2011
Extern gepubliceerdJa


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