Abstract 1149: Prognostic impact of Vasohibin 1 (VASH1) expression in tumor cells of colorectal cancer patients.

Abstract

Abstract Background. Vasohibin 1 (VASH1) is an angiogenesis inhibitor which is expressed in the endothelial cells (ECs) of blood vessels of the tumor stroma. VASH1 expression of tumor stromal ECs has been reported to be associated with poor prognosis of human breast cancer and urothelial carcinoma. High VASH1 expression of tumor cells themselves was also reported to be associated with poor prognosis in hepatocellular carcinoma, whereas low VASH1 in tumor cells correlated with unfavorable clinicopathological features in renal cell carcinoma. Aim. This study aims to investigate the expression of VASH1 in tumor cells using immunohistochemistry and to evaluate its clinical and prognostic significance in patients with colorectal cancer (CRC). Materials and methods. Three hundred and nine (n=309) samples of CRC patients who underwent surgery between 2006 and 2011 were investigated for the expression of VASH1 using standard immunohistochemistry (IHC). The IHC score of VASH1 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 VASH1 in tumor cells and clinicopathological characteristics was analyzed. Impact of VASH1 expression in tumor cells on overall survival (OS) was also analyzed using univariate and multivariate analyses. Results. The number of CRC patients with stage I, II, III, and IV were 65, 91, 82, and 71, respectively. The median follow-up of all patients was 19.0 months (range: 2-77 months). Forty one patients had recurrent disease, and 44 patients had died. In CRC tissues, VASH1 protein was localized mainly in the cytoplasm of tumor cells, and partly in vascular endothelial cells. Imunoreactive VASH1 was detected in tumor cells of 272 CRC patients(88%). High VASH1 expression showed a trend towards an association with degree of differentiation. No significant association between VASH1 expression in tumor cells and the other clinicopathological variables was observed. In univariate analysis, high VASH1 expression was significantly associated with poor prognosis of CRC patients [p=0.02, hazard ratio (HR)=2.21, 95 % CI, 1.13-4.74]. In multivariate analysis, high VASH1 expression retained an independent prognostic factor for CRC patients [p<0.01, hazard ratio (HR)=2.81, 95 % CI, 1.38-6.29].Conclusions. In CRC, tumor cells expressed VASH1 protein detected by IHC. High VASH1 expression in tumor cells has an independent prognostic significance in CRC patients. Citation Format: Takahito Kitajima, Koji Tanaka, Susumu Saigusa, Tadanobu Shimura, Satoru Kondo, Yuji Toiyama, Yoshinaga Okugawa, Yasuhiro Inoue, Masaki Ohi, Toshimitsu Araki, Keiichi Uchida, Yasuhiko Mohri, Hiroki Hori, Masato Kusunoki. Prognostic impact of Vasohibin 1 (VASH1) expression in tumor cells of colorectal cancer patients. [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 1149. doi:10.1158/1538-7445.AM2013-1149