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- Title
Histopathological and molecular features of late relapses in non-seminomas.
- Authors
Mayer, Frank; Wermann, Hendrik; Albers, Peter; Stoop, Hans; Gillis, Ad J. M.; Hartmann, Jörg T.; Bokemeyer, C. Carsten; Oosterhuis, J. Wolter; Looijenga, Leendert H. J.; Honecker, Friedemann
- Abstract
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.
- Subjects
GERM cell tumors; HISTOPATHOLOGY; CANCER relapse; TERATOMA; GENETIC mutation; MICROSATELLITE repeats; DRUG therapy
- Publication
BJU International, 2011, Vol 107, Issue 6, p936
- ISSN
1464-4096
- Publication type
Article
- DOI
10.1111/j.1464-410X.2010.09631.x