EXPRESSION OF THE ETS-1 PROTOONCOGENE IN HUMAN GASTRIC-CARCINOMA - CORRELATION WITH TUMOR INVASION

The proto-oncogene Ets-1 is a transcription factor known to control th e expression of a number of genes involved in extracellular matrix rem odeling and has been postulated to play a role in cell migration and t umor invasion. To elucidate the involvement of Ets-1 in human gastric carcinomas, we examined II cases of gastric adenoma and 110 cases of g astric carcinoma by immunohistochemistry and compared the degree of Et s-1 expression with the depth of carcinoma invasion. Ets-1 was not exp ressed either in the normal gastric epithelium or in gastric adenomas, Among the 110 cases with gastric adenocarcinoma, 70 (63.6%) showed po sitive staining for the Ets-1 protein. In mucosal carcinomas, only 3 o f 26 cases (11.5%) showed positive immunostaining for Ets-1. In contra st, 67 of 84 cases (79.8%) with submucosal or more invasive carcinomas showed immunopositivity and intense staining for Ets-1 in the tumor c ells. The pattern of Ets-1 immunostaining in mucosal carcinomas was we nt and differed from that of other local invasive carcinomas (P < 0.00 1). Histologically, signet-ring cell and mucinous carcinomas expressed relatively weak positivity for Ets-1. Ets-1 expression correlated sig nificantly with the presence of lymph node metastasis (P < 0.001). In situ hybridization, using an Ets-1 oligonucleotide probe, also confirm ed the presence of Ets-1 mRNA in gastric carcinomas. Expression of Ets -1 mRNA was also detected in four different kinds of cultured human ga stric carcinoma cell lines by the reverse transcription polymerase cha in reaction method. These findings suggest that Ets-1 is overexpressed in gastric mucosal cells that have undergone malignant conversion and that Ets-1 is one of the factors involved in the penetration of gastr ic carcinoma beyond the muscularis mucosa.