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Histopathological and molecular features of late relapses in non‐seminomas
Author(s) -
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
Publication year - 2011
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2010.09631.x
Subject(s) - seminoma , malignancy , germ cell tumors , microsatellite instability , histology , germ cell , chemotherapy , pathology , biology , teratoma , yolk sac , kras , histopathology , cancer , medicine , microsatellite , colorectal cancer , embryo , genetics , gene , allele
Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Late relapses from germ cell tumors respond poorly to systemic chemotherapy. This feature has been partly attributed to their presumed derivation from mature teratomas giving rise to secondary non‐germ cell histologies that have lost the original germ cell‐like behaviour. Our series demonstrates the occurrence of non‐germ cell malignancies in the absence of mature teratoma and points towards microsatellite instability and BRAF‐mutations as the biologic basis for chemotherapy resistance in about half of the cases. 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.