Abstract 805: Microarray analysis reveals Versican and CD9 as novel prognostic factors of GIST
Authors: Setoguchi Tomohiko , Kikuchi Hirotoshi , Iino Ichirota , Kawabata Toshiki , Yamamoto Masayoshi , Ohta Manabu , Kamiya Kinji , Baba Megumi , Tanaka Tatsuo , Mori Hiroki , Sugimura Haruhiko , Seto MItsutoshi , Konno HIroyuki 
Published: February 2011

Abstract
Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in GI tract. The cause of GIST is gain-of-function mutation of the c-kit gene in the interstitial cells of Cajal. Recently there are given the opportunity to find incidental small GIST because of development of laparoscopic surgery and acquisition of GIST concept. Most incidental GISTs have been reported to carry the c-kit gene mutation. Therefore it seems that substantial genetic changes other than c-kit are necessary for the development of GIST, and that further genetic changes are involved in the metastatic process. However, those factors regulating metastasis remain to be elucidated. We have previously reported that LOH of the c-kit gene, or chromosome 4q, could be responsible for liver metastasis, but it remains unclear how loss of chromosome 4 enhances such process and whether other oncogenes are involved. The aim of this study is to explore the mechanisms underlying liver metastasis of GIST. Method: To detect the genes up-regulated or down-regulated in the process of liver metastasis, comprehensive microarray analysis was performed using cDNA from three non-metastatic primary GISTs and five metastatic liver GISTs. The data was confirmed by qRT-PCR. To examine protein levels, immunohistochemistry was done using formalin fixed paraffin embedded tissues of 130 GIST. Result: Microarray analysis revealed that expression levels of 202 and 185 genes were higher and lower, respectively, in the metastatic liver GISTs as compared to the primary GIST. Upregulated genes were mainly located in chromosome 1q, 17 and 20, and down-regulated genes were located in 1p, 4q and 15, which were consistent with previous reports including the loss of chromosome 4 in our paper. Versican, known to recruit myeloid-derived mononuclear cells, accelerate immflamatory cytokine such as TNFa and facilitate tumor metastasis, was up-regulated. Cadherin8, Neuronal cell adhesion molecule, Protocadherin10 and CD9 were down-regulated in the metastatic GIST. Protein expression levels of Versican and CD9 were higher and lower in the metastatic liver GIST. Eventually, high immunoreactivity of Versican (n=65) or low immunoreactivitiy of CD9 (n=56) were poor patient's outcome, respectively. (p=0.021 and p&lt;0.01) Conclusion: In addition to the c-kit gene mutation, genetic or epigenetic changes involved in the regulation of adhesion molecules, inflammatory cells and therefore tumor microenvironment play important roles in the process of liver metastasis. Of particular, Versican and CD9 are potential prognostic factors of GIST.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 805.