Abstract 405: Differential gene expressions in primary gastric and intestinal gastrointestinal stromal tumors and metastatic liver tumors.
Authors: Hirotoshi Kikuchi, Tomohiko Setoguchi, Shinichiro Miyazaki, Ichirota Iino, Yoshihiro Hiramatsu, Kinji Kamiya, Manabu Ohta, Takanori Sakaguchi, Hiroyuki Konno
Journal: Cancer Research (2013)

Abstract Background; Gastrointestinal stromal tumor (GIST) is known to originate from the interstitial cells of Cajal or its precursors with an activating mutation in the c-kit gene. On the other hand, it has been shown that micro GIST with c-kit mutation was commonly found in stomach resected for gastric cancer or in autopsy specimens. It seems that c-kit mutation initiates GIST and other genetic or epigenetic changes occur in the developmental process of GIST. In this study, we compared gene expression profiles among gastric and intestinal GIST as well as their metastatic liver tumors to identify the genes involved in the process of malignant transformation of GIST. Methods; Fresh frozen samples of primary gastric and intestinal GISTs and metastatic liver GISTs were used in the analysis. Total RNA was extracted and gene expression levels were compared by microarray analysis between 3 primary gastric GISTs and 4 metastatic liver GISTs, and among 6 primary gastric GISTs, 3 primary intestinal GISTs and 6 metastatic liver GISTs. Protein levels of versican and CD9 were analyzed by immunohistochemistry in 104 primary gastric GISTs and 13 metastatic liver GISTs. Results; Expression levels were higher for 165 genes and lower for 146 genes in metastatic liver GIST compared with primary gastric GIST. Among them, we further focused on two genes; versican and CD9, mRNA levels of which were higher and lower, respectively, in the metastatic liver GIST. Immunohistochemical analysis revealed that protein levels of versican and CD9 were higher and lower, respectively, in metastatic liver tumors compared with primary gastric GIST. High expression of versican and loss of CD9 expression correlated with shorter liver metastasis-free survival after gastrectomy. Microarray analysis of primary gastric and intestinal GISTs and metastatic liver GIST classified them into two groups according their gene expressions. One group consisted of primary gastric GIST without postoperative recurrence and the other consisted of clinically malignant GIST, intestinal GIST and metastatic liver GIST. These data suggest that intestinal GIST, regardless of presence of metastasis, shows gene expression profile similar to clinically malignant GIST and further to metastatic tumors and may explain mechanisms by which intestinal GISTs are more likely to show clinically malignant phenotype than gastric GISTs. Conclusions: Gene expression profile of primary intestinal GIST was similar to that in metastatic liver GIST but not to that in primary gastric GIST. Versican and CD9 could be potential prognostic markers of gastric GIST with which to predict the risk of postoperative liver metastasis. Citation Format: Hirotoshi Kikuchi, Tomohiko Setoguchi, Shinichiro Miyazaki, Ichirota Iino, Yoshihiro Hiramatsu, Kinji Kamiya, Manabu Ohta, Takanori Sakaguchi, Hiroyuki Konno. Differential gene expressions in primary gastric and intestinal gastrointestinal stromal tumors and metastatic liver tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 405. doi:10.1158/1538-7445.AM2013-405 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.