Expression of Annexin A5 Is Associated With Higher Tumor Stage and Poor Prognosis in Colorectal Adenocarcinomas

Goals: To gain an insight into the putative role of annexin A5 (ANXA5) in the tumor stage and its clinical outcome. Background: ANXA5 is a calcium-binding protein, which has been implicated in the carcinogenesis of several carcinomas. However, the role of ANXA5 in colorectal cancer (CRC) is unclear. Study: We investigated the expression of ANXA5 in colorectal adenocarcinoma. This study included 207 consecutive patients with sporadic CRC. Paired colorectal tissue samples and corresponding nonmalignant tissues were obtained by surgical resection. ANXA5 mRNA and protein expression in each tissue were assessed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemical staining. Data were statistically correlated with pathologic parameters and clinical outcome. Results: Real-time reverse transcriptase polymerase chain reaction showed that there is an up-regulation in the mRNA level of ANXAS in tumors (P < 0.001). lmmunohistochemical study revealed that high ANTXA5 expression was present in 40.58% (84 of 207) of tumors. Univariate analysis showed increased ANXA5 expression correlated with pT stage (P = 0.008), liver metastasis (P = 0.024), pathologic tumor-node-metastasis stage (P = 0.015), Dukes' stage (P = 0.017), recurrence (P = 0.024), cancer-related death (P = 0.028), recurrence-free probability (P = 0.003), and overall survival (P = 0.005). Multivariate analysis showed that ANXAS expression and liver metastasis significantly correlated with recurrence-free probability (P = 0.039 and P = 0.048, respectively) and overall survival (P = 0.012 and P = 0.021, respectively) independent of pT stage and pN stage. Conclusions: From these findings ANXA5 expression seems to be related to the tumor stage and clinical outcome of CRC. Thus ANXA5 could serve as a prognostic marker for tumor progression.