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

Abstract

Background Undifferentiated-type early gastric adenocarcinomas are generally classified into two groups: pure undifferentiated-type adenocarcinomas, which naturally develop as undifferentiated-type without a glandular component; and mixed differentiated/undifferentiated-type adenocarcinomas, which are associated with some vestigial glandular component and presumably develop from differentiated-type adenocarcinoma. The differences in phenotypic expression between these two groups were examined using mucin core protein and CDX2. Methods A total of 210 lesions of undifferentiated-type early gastric adenocarcinoma less than 25 mm in diameter were classified into four categories (gastric type, gastrointestinal type, intestinal type, and null type) based on their MUC5AC, MUC6, MUC2, and CDX2 immunoprofiles. Results Gastric type was significantly (p \ 0.01) decreased and gastrointestinal type was significantly (p \ 0.01) increased both in pure undifferentiated-type adenocarcinomas and in mixed differentiated/undifferentiated-type adenocarcinomas when CDX2 was applied to mucin core protein. In the pure undifferentiated-type adenocarcinomas, gastric type decreased and gastrointestinal type increased as tumor size increased (p \ 0.05). In contrast, in the mixed differentiated/undifferentiated-type adenocarcinomas, gastrointestinal type was most common even in small-sized (B10 mm) carcinomas and was generally stable regardless of tumor size. In submucosal carcinomas, gastrointestinal type decreased and gastric type and intestinal type increased during carcinoma invasion from the intramucosal to submucosal parts (p \ 0.05). The positivity rates for all phenotypic markers, especially gastric markers, tended to decrease during submucosal invasion. Conclusions CDX2 is a sensitive marker for assessing intestinal phenotypic expression, and it is likely that there are two different pathways of tumor progression in undifferentiated-type adenocarcinoma of the stomach, according to phenotypic expression.

Mucin phenotype expression of gastric neuroendocrine neoplasms: analysis of histopathology and carcinogenesis

“…As previously reported [10][11][12][13][14][15][16], the distributions and positivity rates of MUC5AC and HGM, as well as those of MUC6 and M-GGMC-1, are different. Furthermore, CDX2 is reported to be closely associated with intestinal phenotype expression in human gastric carcinomas [19][20][21] and a more sensitive marker than MUC2 for assessing the presence of intestinal phenotypic expression in gastric adenocarcinomas from the early stage [22]. We therefore employed each of these markers to accurately determine the mucin phenotype of carcinomas.…”

“…Furthermore, the caudal-type homeobox gene Cdx2 encodes a transcription factor that has been found to play an important role in the mammalian intestine [17,18] and which is reported to demonstrate a close relationship to the intestinal phenotype in gastric adenocarcinomas [19][20][21][22].…”

Gastric mucin expression in first-degree relatives of gastric cancer patients

“…Diffuse-type neoplasms are considered to be poorly differentiated and arise in normal gastric mucosa [2]. Recently, attempts have been made to more accurately classify gastric adenocarcinomas using immununohistochemical staining [3][4][5]. This method identifies surface gastric and small intestinal mucins.…”

Re‐evaluation of Phenotypic Expression in Differentiated‐type Early Adenocarcinoma of the Stomach

“…These findings strongly suggest that phenotype alteration of carcinoma occurs not by the acquisition of a new independent phenotypic expression, but by reduced expression of each phenotype marker during submucosal invasion. Ikarashi et al 33 reported similar phenotype alterations of early undifferentiated-type gastric adenocarcinomas.…”