Different expression pattern and significance of p14ARF-Mdm2-p53 pathway and Bmi-1 exist between gastric cardia and distal gastric adenocarcinoma

Abstract

Recent studies have suggested that adenocarcinoma of gastric cardia (GCA) is distinct from distal stomach, with different risk factors, tumor characteristics, and biological behavior. The aim of this study is to evaluate the possible difference in the expressions of p14ARF, Mdm2, p53, and Bmi-1 by immunohistochemical staining on paraffin-embedded tissues of gastric cardia adenocarcinoma (GCA; n = 74) and distal gastric adenocarcinoma (DGA; n = 41). The results showed that the percentage of p14ARF-negative expression, Mdm2 overexpression, p53-positive expression, and p53 pathway abnormality (p14ARF(-)/Mdm2(+)/p53(+)) were all significantly higher in GCA than those in DGA (P < .05). Further analysis showed that in GCA, the negative expression of p14ARF was significantly associated with poor differentiation, Mdm2 overexpression with tumor stage and lymph node metastasis, and positive p53 expression with tumor stage (P < .05), whereas in DGA, only Mdm2 overexpression was related with well/moderate differentiation (P < .05). Abnormality of the p53 pathway was significantly correlated with poorer differentiation only in GCA (P < .05). The positive expression of Bmi-1 in all cases of GCA and DGA was significantly higher than normal gastric mucosa epithelium, but no difference was found between GCA and DGA (P > .05). Thus, the results in this study confirmed that different expression pattern and clinicopathologic significance of the p14ARF-Mdm2-p53 pathway did exist between GCA and DGA. The results further support the hypothesis that different mechanisms may be involved in the development and progression of adenocarcinoma from cardia and distal portion of stomach.