Abstract 4512: AT rich interactive domain 3A (ARID3A) overexpression correlates with good prognosis in colorectal cancer

Abstract

Abstract AT Rich Interactive Domain 3A (ARID3A) is a member of the ARID family of DNA-binding proteins. Previous studies have shown that ARID3A controls the cell growth through p53-dependent manner, whereas its significance in the prognosis of colorectal cancer (CRC) is not yet fully understood. In this study, formalin-fixed, paraffin-embedded tumors and matched normal mucosae from 690 patients who underwent surgery for CRC were constructed into tissue microarrays. The expression of ARID3A was investigated by immunohistochemistry. We detected a nuclear positive expression of ARID3A in a subset of colorectal cancers, whereas ARID3A was completely negative in all normal mucosae. Of the 690 cases, 195 tumors (28.3%) were strong positive for ARID3A, 187 tumors (27.1%) were weak positive and 308 tumors (44.6%) were negative. We examined p53 expression status by immunohistochemistry simultaneously. Among the 690 tumors, 358 tumors (51.9%) were positive for p53 expression and 332 tumors (48.1%) were negative for p53 expression. Kaplan-Meier method and Cox proportional hazards modeling were used to analyze the overall survival between ARID3A negative or weak expression group and ARID3A strong expression group. The ARID3A expression in CRCs was significantly correlated with age (P=0.003), degree of differentiation (P<0.001), depth of invasion (P=0.001), lymph node metastasis (P=0.008), distant metastasis (P=0.007), TNM stage (P<0.001), status of microsatellite instability (P<0.001), and CEA levels (P=0.003). Moreover, the strong expression of ARID3A and the negativity of p53 were statistically correlated (P=0.045). The survival of CRC patients with ARID3A strong expression was significantly longer than that of patients with ARID3A negative or weak expression (P=0.002), however the effect of ARID3A on the survival rate of CRCs might differ by p53 status. Combined analysis of ARID3A and p53 expression indicated that CRC group with ARID3A-strong positive and p53-negative showed better prognosis compared with the remaining groups (P=0.003). On multivariate analysis, ARID3A overexpression was proven to be an independent predictor for better prognosis in CRC (95% CI: 0.44-0.96; P=0.031). In conclusion, this study strongly suggests the usefulness of ARID3A as a biomarker to predict the prognosis of colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4512. doi:1538-7445.AM2012-4512