Expression And Significance Of RegIV In Gastric Neoplastic And Nonneoplastic Tissues

OBJECTIVE To investigate the expression and significance of RegIV( regenerating islet-derived family member 4) protein in gastric neoplastic and nonneoplastic tissues.METHOD RegIV protein was detected with immunohistochemiscal (IHC) methods in 73 GC specimens that were collected from surgical resection in our hospital and a tissue microarray(TMA) of 90 GC specimens with adjacent non-neoplastic mucosa.RESULTS RegIV was selectively expressed in the parietal cells of gastric mucosa, and was absent in foveolar epithelial cells. In intestinal metaplasia (IM) of the stomach, goblet cells were strongly positive for RegIV (positive rate 100%). Intestinal gastric carcinomas (with goblet cells present), gastric signet ring cell carcinomas (SRCCs) and mucinous adenocarcinomas showed frequently immunoreactivity (100%(3/3),93.3%(14/15)and 90.9%(10/11)respectively). Neuroendocrine cells at the base of intestinal metaplasia were strongly perinuclear positive for Reg IV, none of the 6 cases of gastric neuroendocrine neoplasm showed RegIV staining. No association of Reg IV expression with aggressive parameters of gastric carcinoma, including invasion, metastasis, or TNM staging was found ( P>0.05 ) .However, RegIV expression was associated with histopathological subtype(sP<0.05). The expressive difference of RegIV in intestinal and diffusetype gastric carcinoma was of statistical significance. The staining pattern of tissue microarray of the stomach was similar to that of paraffin tissue sections collected from our hospital. None of 30 cases of gastric tubular adenocarcinoma was positive for RegIV(positive rate 0%).The positive rate of RegIV expression in gastric mucinous adenocarcinomas and SRCCs were 43.3%(13/30)and 40.0%(12/30)respectively, which were apparently different from that of specimens supported by our hospital.CONCLUSION Goblet cells of intestinal metaplasia of the stomach,gastric SRCCs and mucinous adenocarcinomas expressed Reg IV more frequently than other histologic subtypes, indicating that Reg IV might be involved in the molecular mechanisms of gastric carcinogenesis from IM and globoid dysplasia to adenocarcinoma. Whether Reg IV expression is associated with the neuroendocrine differentiation in gastric carcinoma needs to be confirmed. No association of Reg IV expression with clinicopathological features of patients with gastric cancer was found, however, the potential role of RegIV in invasive behavior of malignant cells could not be excluded completely. The inconsistent IHC results detected in 2 sources of tissues were considered to be associated with many factors such as arealvariation.