Tissue microarray analysis reveals strong clinical evidence for a close association between loss of annexin A1 expression and nodal metastasis in gastric cancer

Aims Annexin A1 (ANXA1) is a calcium- and phospholipid-binding protein that has been implicated in the regulation of inflammation, cell proliferation, and apoptosis. Its role in tumor development and progression is controversial, whereas its role in gastric cancer is unknown. We investigated ANXA1 expression and determined its clinical significance in gastric cancer. Methods and results Tissue microarray blocks containing primary gastric cancer, lymph node metastasis, and adjacent normal mucosa specimens obtained from 1,072 Chinese patients were constructed. Expression of ANXA1 in these specimens was analyzed using immunohistochemistry. Complete loss of ANXA1 expression was observed in 691 (64%) of the 1,072 primary tumors and 146 (86%) of 169 nodal metastases. Loss of ANXA1 expression was significantly associated with advanced T stage, lymph node metastasis, advanced disease stage, and poor histological differentiation. Loss of ANXA1 expression correlated significantly with poor survival rates in both univariate and multivariate analyses. Conclusions ANXA1 expression decreased significantly as gastric cancer progressed and metastasized, suggesting the importance of ANXA1 as a negative biomarker for gastric cancer development and progression.