Japanese Journal of Clinical Oncology Advance Access originally published online on February 1, 2006
Japanese Journal of Clinical Oncology 2006 36(2):85-92; doi:10.1093/jjco/hyi227
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© 2006 Foundation for Promotion of Cancer Research
Chromosomal Numerical Abnormality Profiles of Gastrointestinal Stromal Tumors
1 Department of Pathology and 2 Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, 3 Department of Pathology, Shizuoka Saiseikai General Hospital, Shizuoka, 4 Department of Pathology, Hamamatsu Medical Center, Hamamatsu, Shizuoka, 5 JOKO Corporation, Hongo, Bunkyo-ku, Tokyo, 6 Department of Digestive Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, 7 Department of Genome Science, RCAST, Tokyo, 8 Department of Pathology and Laboratory Medicine, Iwata City Hospital, Iwata, Shizuoka and 9 Information System Division, Biosafety Research Center, Foods, Drugs, and Pesticides, Iwata, Shizuoka, Japan
For reprints and all correspondence: Haruhiko Sugimura, Department of Pathology, Hamamatsu University School of Medicine, 1-20-1, Handayama, Hamamatsu, Shizuoka 431-3192, Japan. E-mail: hsugimur{at}hama-med.ac.jp
Received June 17, 2005; accepted December 1, 2005
Background: Biological variations in and the heterogeneity of gastrointestinal stromal tumors (GISTs) are well known, but chromosomal numerical abnormality (CNA) has not been fully examined especially in this context. The aim of this study is to test CNA as a possible biological predictor of biological behavior of GISTs.
Method: We applied microwave-assisted FISH protocol to pathological archives of GIST tumors displaying different clinical features to characterize the CNA profile of these tumors. A panel of 18 centromere enumeration probes (CEP) and 24 bacterial artificial chromosome (BAC) or P1-derived artificial chromosome (PAC) probes containing genes like Aurora kinases (AURKs) and other candidate genes involved in human carcinogenesis were used. CNA profiles, histopathological risk categorization and Ki-67 labeling indexes of 23 primary and/or metastatic GIST tumors of 12 subjects (both primary and metastatic in 7 subjects) were compared between primary GIST with and without metastases, and between metastatic and primary portions in 7 individuals.
Results: CNA in the primary sites was more extensive in the GISTs with recurrence and metastasis than in those without, especially as to the loss of chromosome 20 and genomic imbalance of AURKA-containing BAC probe on 20q in the cases with metastasis. The consistent loss of one allele of chromosome 14q was also noted. Interestingly, both primary and metastatic tumors in identical individuals had similar CNA profiles.
Conclusion: The extent of CNA differed between GISTS with and without recurrence or metastasis; thus, FISH analysis of specimens from the primary sites may predict the biological behavior of this tumor.
Key Words: chromosomal numerical abnormality • chromosomal instability • GIST • FISH • microwave
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