Intestinalization of gastric signet ring cell carcinomas with progression

Abstract

Recent developments in mucin histochemistry and immunohistochemistry have made reliable determination of the gastric and intestinal phenotypes of gastric carcinoma cells possible. Phenotypic expression changes from gastric epithelial cell type to intestinal epithelial cell type with the growth of gastric tumours in experimental animals. We studied cell differentiation in gastric signet ring cell carcinomas with progression in 203 surgically obtained specimens. The results showed that the proportion of gastric phenotype carcinomas, in which over 90% of the tissue consists of gastric epithelial cell type cells, decreases with the depth of invasion. The proportion of mixed phenotype carcinomas (between 10% and 90% of the tissue made up of gastric and/or intestinal epithelial cell type cells) increases. The intestinal phenotype (over 90% intestinal epithelial cell type carcinoma cells) was found in four carcinomas (about 2%) involving the serosa. No clear relationship was evident between phenotypic expression of carcinoma cells and the degree of intestinal metaplasia of the surrounding mucosa. Progression of gastric signet ring cell carcinomas is associated with a phenotypic shift from gastric to intestinal type expression.

N‐Methyl‐N‐nitrosourea Concentration‐dependent, Rather than Total Intake‐dependent, Induction of Adenocarcinomas in the Glandular Stomach of BALB/c Mice

“…[29][30][31][32][33] By sequential observation of rat glandular stomach carcinomas and comparisons of phenotypic expression of human gastric carcinoma cells between early and advanced cases, a phenotypic shift from gastric to intestinal epithelial cell type expression has been recognized with progression of each histological type of gastric carcinomas. [33][34][35][36] The present results regarding phenotypic expression of tumor cells showed that mouse glandular stomach adenomas and carcinomas consist solely of tumor cells of gastric epithelial cell type, without any intestinal metaplasia in the mucosa surrounding carcinomas. Thus, differentiated and undifferentiated type carcinomas arise from gastric proper mucosa independently of intestinal metaplasia in this model.…”

Re-evaluation of phenotypic expression in undifferentiated-type early gastric adenocarcinomas using mucin core protein and CDX2

“…These findings may suggest that the increased proportion of I type during submucosal invasion is caused not by the acquisition of intestinal marker expression, but by a reduction of gastric marker expression. In contrast, previous reports have shown that the phenotype of signet-ring cell carcinomas alters from gastric phenotype to intestinal phenotype during submucosal invasion [11][12][13]. It may be argued that reduced gastric phenotypic expression in the submucosal part could be caused by the selective submucosal invasion of constitutively non-gastrictype cells.…”

“…Previous investigations of the phenotypic expression of undifferentiated-type adenocarcinomas are limited, and it has been reported that there are some undifferentiated-type adenocarcinomas of intestinal phenotype [9,10], and that the intestinal phenotype in gastric signet-ring cell carcinomas appears to occur during tumor progression [11][12][13] or during tumor spread in the mucosa [14]. However, how frequent and when phenotypic alteration occurs during the development of undifferentiated-type adenocarcinomas remain controversial.…”

Correlation between Magnifying Narrow-band Imaging Endoscopy Results and Organoid Differentiation Indicated by Cancer Cell Differentiation and its Distribution in Depressed-Type Early Gastric Carcinoma

“…On the other hand, 18 of 19 cases with the CSP were undifferentiated adenocarcinoma, and 17 of these had a gastric component, and no I-type was found in this study. Since I-type early undifferentiated adenocarcinoma is very rare (Yamachika et al, 1997), its vascular construction is unclear. Further accumulation of cases of I-type early undifferentiated adenocarcinoma in the future may clarify whether the CSP is characteristic of G-type undifferentiated adenocarcinoma or of all types including I-types of undifferentiated adenocarcinoma.…”

“…Tumor cells were functionally (mucus productivity) well differentiated, although the glandular duct structure was undifferentiated. Early undifferentiated gastric cancer is comprised of the G-type and I-type cancer cells, which increase with progression (Yamachika et al, 1997) while organoid differentiation may be lost. Therefore, the CSP is characteristic of the early stage of G-type undifferentiated adenocarcinoma.…”