Expression of the Ets-1 proto-oncogene in human gastric carcinoma: correlation with tumor invasion.
The proto-oncogene Ets-1 is a transcription factor known to control the expression of a number of genes involved in extracellular matrix remodeling and has been postulated to play a role in cell migration and tumor invasion. To elucidate the involvement of Ets-1 in human gastric carcinomas, we examined 11 cases of gastric adenoma and 110 cases of gastric carcinoma by immunohistochemistry and compared the degree of Ets-1 expression with the depth of carcinoma invasion. Ets-1 was not expressed either in the normal gastric epithelium or in gastric adenomas. Among the 110 cases with gastric adenocarcinoma, 70 (63.6%) showed positive staining for the Ets-1 protein. In mucosal carcinomas, only 3 of 26 cases (11.5%) showed positive immunostaining for Ets-1. In contrast, 67 of 84 cases (79.8%) with submucosal or more invasive carcinomas showed immunopositivity and intense staining for Ets-1 in the tumor cells. The pattern of Ets-1 immunostaining in mucosal carcinomas was weak and differed from that of other local invasive carcinomas (P < 0.001). Histologically, signet-ring cell and mucinous carcinomas expressed relatively weak positivity for Ets-1. Ets-1 expression correlated significantly with the presence of lymph node metastasis (P < 0.001). In situ hybridization, using an Ets-1 oligonucleotide probe, also confirmed the presence of Ets-1 mRNA in gastric carcinomas. Expression of Ets-1 mRNA was also detected in four different kinds of cultured human gastric carcinoma cell lines by the reverse transcription polymerase chain 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 gastric carcinoma beyond the muscularis mucosa.
Nakayama
T
T
Department of Pathology, Nagasaki University School of Medicine, Japan.
Ito
M
M
Ohtsuru
A
A
Naito
S
S
Nakashima
M
M
Fagin
J A
JA
Yamashita
S
S
Sekine
I
I
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000236:Adenoma / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D015682:Retroviridae Proteins, Oncogenic; C050379:oncogene proteins v-ets