Yamashita Kimihiro, Igarashi Hisaki, Kitayama Yasuhiko, Ozawa Takachika, Kiyose Shinichiro, Konno Hiroyuki, Kazui Teruhisa, Ishikawa Shumpei, Aburatani Hiroyuki, Tanioka Fumihiko, Suzuki Masaya, Sugimura Haruhiko
Department of Pathology, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan.
Jpn J Clin Oncol. 2006 Feb;36(2):85-92. doi: 10.1093/jjco/hyi227. Epub 2006 Feb 1.
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.
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.
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.
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.
