Annals of Oncology 13:1656-1664, 2002
© 2002 European Society for Medical Oncology
Original Paper |
Population-based genetic alterations in Ewing’s tumors from Japanese and European Caucasian patients
1 Department of Orthopaedics, 2 Gerhard-Domagk-Institute of Pathology and 4 Pediatric Hematology and Oncology, Westfaelische Wilhelms-University, Münster, Germany; 3 Department of Orthopaedic Surgery and 5 Department of Pathology, National Cancer Center Hospital, Tokyo; 6 Research Institute, National Cancer Center, Tokyo; 7 Department of Orthopaedic Surgery, Okayama University Medical School, Okayama, Japan; 8 Institute of Pathology, Kempten; 9 Institute of Pathology, Heinrich-Heine-University, Düsseldorf, Germany
Received 23 November 2001; revised 8 February 2002; accepted 7 March 2002
Background:
The incidence of Ewing’s tumors (ETs) is lower in Asians or African-Americans than in Caucasians.
Patients and methods:
Japanese ETs were available for analysis of chromosomal aberrations by comparative genomic hybridization (n = 16) and for expression of chimeric EWS transcripts by reverse-transcriptase polymerase chain reaction (n = 11). These results in Japanese patients were compared with those of 62 ETs in European Caucasian patients registered in the European Intergroup Cooperative Ewing’s Sarcoma Study.
Results:
Japanese patients with ET had lower overall survival (P = 0.0446) and relapse-free survival (P = 0.0371) compared with European Caucasian patients. Ten of 11 Japanese ETs and 31 of 62 European Caucasian ETs had type I (EWS exon 7 to FLI1 exon 6) fusion transcripts. In Japanese ETs, the median numbers of chromosomal aberrations were 2.0 and 6.0 in 11 primary tumors and five relapsed tumors, respectively. In European Caucasian ETs, the median number of changes were 2.5 and 5.0 in 52 primary and 10 relapsed tumors, respectively. Frequent gains were 8q (38%), 8p (31%) and 12q (25%) in Japanese ETs and 8q (52%), 8p (48%) and 12q (19%) in European Caucasian ETs. Frequent losses were 19q (44%), 19p (38%) and 17p (25%) in Japanese ETs and 16q (21%), 19q (18%) and 17p (15%) in European Caucasian ETs. The incidence of losses of 19p (P = 0.0215) and 19q (P = 0.0277) were significantly higher in Japanese ETs than in European Caucasian ETs. An amplification (1p33-p34) was observed in only one Japanese ET.
Conclusions:
Japanese patients with ET in this study had a worse prognosis than European Caucasian patients. In molecular genetic analyses, Japanese ETs had a higher frequency of loss of chromosome 19 than European Caucasian ETs. Different genetic aberrations may explain the different incidences and prognoses of ET between Caucasian and Japanese patients.
Key words: Ewing’s tumor prognosis, Caucasian, c-erbB-2, comparative genomic hybridization, chromosomal aberrations, Japanese