Histopathological and molecular features of late relapses in non-seminomas.
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Histopathological and molecular features of late relapses in non-seminomas. / Mayer, Frank; Wermann, Hendrik; Albers, Peter; Stoop, Hans; Gillis, Ad J M; Hartmann, Jörg T; Bokemeyer, Carsten; Oosterhuis, J Wolter; Looijenga, Leendert H J; Honecker, Friedemann.
In: BJU INT, Vol. 107, No. 6, 6, 2011, p. 936-943.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Histopathological and molecular features of late relapses in non-seminomas.
AU - Mayer, Frank
AU - Wermann, Hendrik
AU - Albers, Peter
AU - Stoop, Hans
AU - Gillis, Ad J M
AU - Hartmann, Jörg T
AU - Bokemeyer, Carsten
AU - Oosterhuis, J Wolter
AU - Looijenga, Leendert H J
AU - Honecker, Friedemann
PY - 2011
Y1 - 2011
N2 - Study Type - Therapy (case series) Level of Evidence 4 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. CONCLUSION: 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.
AB - Study Type - Therapy (case series) Level of Evidence 4 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. CONCLUSION: 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 107
SP - 936
EP - 943
JO - BJU INT
JF - BJU INT
SN - 1464-4096
IS - 6
M1 - 6
ER -
