Immunohistochemically detectable Cdx2 is present in intestinal phenotypic elements in early gastric cancers of both differentiated and undifferentiated types, with no correlation to non‐neoplastic surrounding mucosa

Abstract

It has previously been reported that Cdx2 is the useful prognostic and intestinal phenotypic marker in advanced gastric cancers (GC). In this study, Cdx2 expression and phenotype in early GC and non-neoplastic surrounding mucosa were examined. A total of 130 early GC (70 intramucosal and 60 submucosally invasive cancers) histologically and phenotypically were evaluated. The expression of Cdx2 was assessed by immunohistochemistry. The lesions were phenotypically divided into 44 gastric (G), 42 gastric and intestinal mixed (GI), 30 intestinal (I), and 14 null (N) types, independent of the histological classification. Most of the early GC were Cdx2-positive, nuclear staining being strongly associated with intestinal phenotypic expression. Early differentiated cancers tended to feature both Cdx2 and intestinal phenotypic expression, while their undifferentiated counterparts were more likely to demonstrate only gastric phenotypic expression (P < 0.05). The phenotypes of six intramucosal microcarcinomas did not correlate with those of adjacent normal glands. These data suggest that Cdx2 is expressed in the very early stage of gastric carcinogenesis in association with the shift from gastric to intestinal phenotypic expression. This appears to occur in differentiated cancers at an earlier stage than in undifferentiated ones, and may be linked to suppression of expansion of malignant cells.

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

“…Previous reports have shown the rates of the G, GI, I, and N types of early undifferentiated-type adenocarcinoma, including signet-ring cell carcinoma, to be 27.8-62.4 %, 24.7-68.5 %, 0-23.1 %, and 0-10.8 %, respectively [9,10,13,14,17,26]. In contrast to the above findings based on MUC only, PURE-type carcinomas in the present study were classified into 17.9 % (19/106) G type, 78.3 % (83/ 106) GI type, 1.9 % (2/106) I type, and 1.9 % (2/106) N type based on MUC and CDX2.…”

“…The positivity rate was higher for CDX2 than for MUC2, and CDX2 expression was detected in cancerous areas not only where MUC2 expression was apparent, but also in tissues exhibiting only gastric markers or null phenotypic lesions. Previous reports have shown that there is a positive correlation between CDX2 expression and MUC2 [21,33], and that CDX2 expression might precede intestinal phenotypic expression during a shift from gastric to intestinal phenotype with the progression of gastric carcinomas [17]. Thus, CDX2 appears to be a more sensitive marker than MUC2 for assessing the presence of intestinal phenotypic expression.…”

“…On the other hand, there are some reports [17][18][19]33] suggesting a possible tumor suppressor role for CDX2, but the significance of CDX2 expression in gastric neoplasms is still under debate. The present study targeted the expression of mucin phenotype, and the materials used were limited to early-stage gastric carcinomas sized 25 mm or less, which made it difficult to evaluate biological PURE-type carcinomas showed the gastric phenotype in 32.1 % of cases when their size was B10 mm, considered to be a very early stage of carcinogenesis.…”

“…The caudalrelated homeobox gene CDX2 is important for the maintenance of intestinal epithelial cells [15], and there have been several reports of CDX2 expression in human gastric carcinomas and intestinal metaplasia [16][17][18][19][20]. It has previously been shown that CDX2 is closely associated with intestinal phenotypic expression in gastric carcinomas [17][18][19]21].…”

“…It has previously been shown that CDX2 is closely associated with intestinal phenotypic expression in gastric carcinomas [17][18][19]21]. However, few studies have evaluated phenotypic expression in undifferentiated-type adenocarcinoma and/or signet-ring cell carcinoma using CDX2 as a phenotypic marker [16,17,22,23].…”