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

Abstract

A total of 313 cases of differentiated-type early gastric adenocarcinomas, including 113 cases of small-sized carcinoma (5< × ≤10 mm) and 121 cases of microcarcinoma (0< × ≤5 mm), were examined immunohistochemically to clarify the phenotypic expressions. They were classified into four categories (gastric phenotype (G-type), intestinal phenotype, gastrointestinal phenotype, and null phenotype) by a two-step process: the phenotype based on an immunoprofile of mucin core proteins (MUCs) with CDX2 (w/.CDX2-assessment); and the phenotype of MUCs only (w/o.CDX2-assessment). CDX2 expression was observed in 89.1% (279/313); it was highly expressed in 87.6% (106/121) of microcarcinomas. MUC2 expression increased as tumor size increased (P < 0.05). Compared with w/o.CDX2-assessment, w/.CDX2-assessment showed significantly fewer G-type carcinomas (P < 0.05). Each phenotype marker was less expressed in the submucosal part than in the mucosal part. In conclusion, CDX2 was a sensitive marker for assessing intestinal phenotype. A large portion of the early differentiated-type adenocarcinomas expressed CDX2 from the very early stage of carcinogenesis, and the proportion of G-type was unexpectedly low. Lower expression of each phenotype marker was considered the cause of phenotype alteration during submucosal invasion.

A comprehensive review of the ten main platelet receptors involved in platelet activity and cardiovascular diseaseUnique immunohistochemical profiles of MUC5AC, MUC6, P53, and Ki67 in gastric atypical hyperplasia and dysplasia

“…Gastric cancer mucin phenotypes, categorized into intestinal, gastric, combined, and unclassified types based on the expression of these markers, have varied implications for malignancy [18]. Notably, gastric-type mucin phenotypes are critical to identify due to their increased malignant potential in early invasion and metastasis stages [19]. Abnormal expression or absence of mucin distribution can signal abnormal differentiation and maturation of gastric mucosal glands, serving as a molecular marker for malignant malignancy [20,21].…”

Green epithelium revealed by narrow-band imaging (NBI): a feature for practical assessment of extent of gastric cancer after H. pylori eradication

“…CDX2 is an intestine-specific transcription factor that is reportedly important for development and maintenance of the intestinal epithelium 4 , being closely associated with intestinal phenotypic expression in human gastric carcinomas and intestinal metaplasia 8 9 10 11 12 13 14 15 . In addition, it has been reported that CDX2 has both tumor suppressor 10 11 12 13 14 15 and oncogenic activities 14 , although it remains unclear whether it has an oncogenic role in gastric carcinogenesis. Furthermore, CDX2 is a more sensitive marker than MUC2 or CD10 for assessing presence of an intestinal phenotype from the very early stage of carcinogenesis 9 .…”

“…Furthermore, CDX2 is a more sensitive marker than MUC2 or CD10 for assessing presence of an intestinal phenotype from the very early stage of carcinogenesis 9 . Hayakawa et al reported that CDX2 expression was evident in 89.1 % of 313 cases of intestinal-type (by Lauren’s classification 16 ) early gastric adenocarcinoma 10 . In the current study, CDX2 expression was observed in 95 % (40 of 42) of cases, thus supporting its relationship to oncogenic activity in the stomach.…”

<p>Mucin phenotype of differentiated early gastric cancer: an immunohistochemistry study supporting therapeutic decision making</p>

“…In literature, the incidence of differentiated ECG foveolar-phenotype (DEGC) appears to be 7.9%–23.9% 11. Gastric-type mucin phenotypes should be distinguished from the other DEGC types because of their increased malignant potential in the incipient phases of invasion and metastasis 12. Early foveolar-phenotype differentiated adenocarcinomas tend to be significantly larger tumors and exhibit higher rates of submucosal invasion than the intestinal-phenotype 13.…”