Immunostaining of gastric cancer with neuroendocrine differentiation: Reg IV-positive neuroendocrine cells are associated with gastrin, serotonin, pancreatic polypeptide and somatostatin.

We previously reported that Reg IV is associated with neuroendocrine (NE) differentiation in gastric cancers. The aim was to examine which NE hormone products are related to Reg IV-positive NE cells and their roles in gastric cancers. In the present study, we performed immunohistochemical analysis in a tissue microarray (TMA) of a consecutive series of 630 cases with ten different antibodies, including chromogranin A, synaptophysin and neural cell adhesion molecule (NCAM) as NE differentiation markers, and gastrin, serotonin, calcitonin, gastrin-releasing peptide (GRP), pancreatic polypeptide (PP), somatostatin and glucagon as NE hormones. In 630 cases, we identified 205 (33%) with NE differentiation and 147 (23%) positive for Reg IV. Reg IV-positive cases showed NE differentiation more frequently than Reg IV-negative cases (P < 0.0001). In 205 cases with NE differentiation, Reg IV-positive cases expressed serotonin (P= 0.0032) and somatostatin (P= 0.036) more frequently than Reg IV-negative cases. Double immunofluorescence staining revealed co-expression of Reg IV with gastrin, serotonin and PP. These results indicate that Reg IV might be a mediating factor of several NE hormones.