Nuclear Localization of Annexin A1 Correlates With Advanced Disease and Peritoneal Dissemination in Patients with Gastric Carcinoma

Abstract

Annexin A1 (ANXA1) is a multifunctional molecule, which mediates various important physiologic processes depending on its subcelluar localization. The purpose of this study was to investigate the expression of ANXA1 level and its subcellular localization in paired clinical samples of gastric adenocarcinoma and adjacent normal counterpart. The study also assesses the clinical significance of ANXA1 subcelluar localization in gastric adenocarcinoma. A total of 104 paired resected gastric adenocarcinoma and corresponding normal specimens were collected in this study. Expression of ANXA1 was examined by immunohistochemical staining. Both cytoplasmic and nuclear ANXA1 expression levels and their correlation with clinicopathological parameters were assessed. ANXA1 protein expression was positive in 72 of 104 (69.2%) normal tissues and 47 of 104 (45.2%) gastric adenocarcinoma tissues. ANXA1 staining was predominantly localized in the cytoplasm in all 72 ANXA1-positive normal specimens, whereas 12 ANXA1-positive gastric adenocarcinoma specimens showed positive nuclear staining. The positive nuclear staining correlated well with serosal invasion, peritoneal dissemination and TNM stage. Cases with positive nuclear staining presented more peritoneal dissemination (41.7%, 5/12) than those with negative nuclear staining (8.7%, 8/92; P = 0.007). A logistic regression model revealed that positive ANXA1 nuclear staining had an independent association with peritoneal dissemination (P = 0.039; hazards ratio, 9.499; 95% confidence interval, 1.159-77.815). These results indicated that ANXA1 is expressed in both gastric adenocarcinoma and normal tissues. In gastric adenocarcinoma tissues ANXA1 is expressed both in cytoplasm and nucleus and its nuclear localization correlates with advanced disease stage and peritoneal dissemination.