Abstract
Abstract Background. Angiopoietin-like protein 2 (ANGPTL2) is a secreted protein belonging to the angiopoietin family.It has been reported to act as a causative mediator of chronic inflammation andmetabolic abnormalities. In ovarian and lung cancer, ANGPTL2 expression in tumor cells was reported to be associated with unfavorable prognosis. So far,clinical and prognostic significance of ANGPTL2 in human gastric cancer remains unknown. Aim. This study investigated the expression of ANGPTL2 in tumor cells using immunohistochemistry and to evaluate its clinical and prognostic significance in patients with human gastric cancer (GC). Materials and methods. Two hundred and eighty two (n=282) samples of GC patients were investigated for the expression of ANGPTL2 in tumor cells using standard immunohistochemistry (IHC). The IHC score of ANGPTL2 in tumor cells was determined on the basis of both staining intensity and the percentage of positive cells. The IHC score was dichotomized at the cutoff value predictive of overall survival using a non-parametric receiver operating characteristic analysis. The association between the expression of ANGPTL2 intumor cells and clinicopathological features was analyzed. Impact of ANGPTL2 expression in tumor cells on overall survival (OS) was also analyzed usingunivariate and multivariate analyses. Results. ANGPTL2 protein was localized mainly in the cytoplasm of tumor cells, and partly in the nucleus. High cytoplasmic ANGPTL2 was significantly associated with higher age (p=0.04), larger tumor size (p <0.01), well differentiated histology (<0.01), advanced T stage (p<0.01), lymphovascularinvasion (p <0.01), lymph node involvement (p <0.01), synchronous liver metastasis (p<0.01), and advanced UICC stage (p <0.01). Twenty-four patients (8.5%) showed higher cytoplasmic ANGPTL2 staining at the tumor invasive margin, as compared with the tumor center. In univariate analysis, high cytoplasmic ANGPTL2 and higher cytoplasmic ANGPTL2 at the invasive margin were significantly associated with poor prognosis (p <0.01). In multivariate analysis, both high cytoplasmic ANGPTL2 and higher cytoplasmicANGPTL2 at the invasive margin retained an independent prognostic factor for GC patients [hazard ratio (HR)=2.67 (p=0.014) and 2.54 (p=0.015), respectively]. Conclusions. Tumoral ANGPTL2 expression was associated with gastric tumor progression. Increased ANGPTL2 at both tumor center and invasive margin were independent prognostic indicators in patients with gastric cancer. Citation Format: Tadanobu Shimura, Koji Tanaka, Susumu Saigusa, Satoru Kondo, Takahito Kitajima, Yuji Toiyama, Yoshinaga Okugawa, Yasuhiro Inoue, Toshimitsu Araki, Keiichi Uchida, Yasuhiko Mohri, Tsutomu Nobori, Masato Kusunoki. Prognostic value of angiopoietin-like protein 2 (ANGPTL2) at the tumor margins in patients with gastric cancer. [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 1139. doi:10.1158/1538-7445.AM2013-1139
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