Expression and prognostic significance of gastric-specific annexin A10 in diffuse- and intestinal-type gastric carcinoma

Background and Aims: Annexin A10 (ANXA10) and its liver-specific short isoform (ANXA10S) had tissue-restricted expression. The downregulation of ANXA10S is correlated with tumor progression and poor prognosis in hepatocellular carcinoma. The aim of the present study was to validate the tissue distribution and explore the role of the ANXA10 protein expression in gastric carcinoma. Methods: We examined the ANXA10 protein expression in human and animal tissues and 356 resected primary gastric carcinomas, using specific mouse and rabbit polyclonal antibodies, by immunohistochemical staining. Results: The ANXA10 protein is a nuclear protein specifically expressed in fetal and adult gastric mucosa and Brunner's gland across species, including humans, minipigs, woodchucks, and mice, and is commonly lost in gastric mucosa with intestinal metaplasia. The ANXA10 protein was expressed in 43.5% (155 cases) of gastric carcinomas; 74.2% (98/132) in the diffuse-type gastric carcinoma (DGC), 73.7% (28/38) in the mixed-type gastric carcinoma, and significantly lower in the intestinal-type gastric carcinoma (IGC) and indeterminate groups, 16.8% (28/167) and 5.3% (1/19), respectively (P < 1 x 10-8). IGC with ANXA10 expression was correlated with a higher stage (P = 0.049), particularly higher in stage IIIA/IIIB/IV IGC than lower-stage (IA/IB/II) tumors (P = 0.005), but was not correlated with age, sex, and nodal status. In contrast, DGC with ANXA10 expression was associated with younger age, female patients, and importantly, lower tumor stage and lymph node metastasis (P = 0.007, P = 0.065, P = 0.024, and P = 0.0014, respectively). Moreover, DGC with ANXA10 expression had a better 5-year patient survival (P = 0.0048), whereas IGC with ANXA10 expression had a lower 5-year survival (P = 0.034). Conclusions: The ANXA10 protein expression is a novel marker of gastric differentiation, and is differentially expressed in IGC and DGC, with opposite prognostic significance.