Expression of the SRY-related HMG box protein SOX2 in human gastric carcinoma.

SOX2, a SRY-related HMG box protein, is thought to be an important transcription factor during organogenesis, including the stomach although the expression and function are unclear. We investigated SOX2 protein expression to clarify its roles in differentiation and carcinogenesis of the stomach. Using polyclonal SOX2 antibodies, expression of SOX2 in gastric normal mucosae, intestinal metaplasia and carcinomas from 68 gastric carcinoma patients was studied by immuohistochemistry. SOX2 was strongly and moderately expressed in the nuclei of the foveolar epithelium and intestinal metaplasia, respectively, the expression being much higher than that in carcinomas (p<0.0001). Using antibodies to MUC5AC, MUC2 and CD10, the 68 gastric carcinomas were classified into gastric type, intestinal type, mixed gastric and intestinal type, and null type. A significant difference in SOX2 expression was observed between the gastric and intestinal types (p<0.05), with a higher expression in the former than in the latter. Moreover, over-expression of SOX2 induced the mRNA expression of endogenous MUC5AC, a specific mucin marker for the gastric type, in COS-7 cells. Our findings indicate that SOX2 may play a role in differentiation of the human gastric epithelium, and that SOX2 may be involved in gastric carcinogenesis, particularly in the gastric type.