Metastatic adenocarcinoma from an unknown primary site is a common clinical problem. Determining the cytokeratin (CK) 7/CK20 pattern of tumors is one of the most helpful procedures for this purpose since the CK7-/CK20+ pattern is typical of colorectal adenocarcinomas. CDX2, a critical nuclear transcription factor for intestinal development, is expressed in intestinal epithelium and adenocarcinomas. In the present study, we compared the sensitivity and specificity of CDX2 expression and the CK7-/CK20+ phenotype in differentiating colorectal adenocarcinomas from pancreatic and gastric adenocarcinomas. CK7/CK20 staining pattern and CDX2 expression were evaluated in 118 cases of colorectal, 59 cases of gastric, and 32 cases of pancreatic adenocarcinomas. The sensitivity, specificity, and positive and negative predictive values of the CK7-/CK20+ phenotype and of CDX2 expression were analyzed. The CK7-/CK20+ immunophenotype was expressed by 75 of 118 (64%) colorectal and 3 of 59 (5%) gastric tumors and was not observed in any pancreatic adenocarcinomas. The CK7+/CK20+ immunophenotype was expressed in 24/118 (20%) of colon, 28/59 (48%) of gastric and 7/32 (22%) of pancreatic adenocarcinomas. The CK7+/CK20- expression pattern was observed in only 2% (2 of 118) of colorectal carcinomas. CDX2 was expressed in 114 of 118 (97%) colorectal, 36 of 59 (61%) gastric, and 5 of 32(16%) pancreatic adenocarcinomas. There was no significant association between CDX2 expression and tumor differentiation in colorectal carcinomas. In gastric carcinomas, CDX2 expression was more common in intestinal type tumors than in diffuse type carcinomas. The CK7-/CK20+ phenotype showed a specificity of 96.7% in predicting colorectal adenocarcinomas, which was superior to that of CDX2 expression. CDX2 expression at both cut-off levels (> 5% and > 50%) had a higher sensitivity (96.6% and 78%) than the CK phenotype. Both the CK7-/CK20+ phenotype and expression of the antibody CDX2 are highly specific and sensitive markers of colorectal origin. CDX2 expression should be a useful adjunct for the diagnosis of intestinal adenocarcinomas, particularly when better established markers such as CK7 and CK20 yield equivocal results. The CK7-/CK20+ phenotype is superior in its specificity and positive predictive value and might be preferred. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4851011866354821

/pdf/the-value-of-cdx2-and-cytokeratins-7-and-20-expression-in-4zajx9mqy5.pdf

The value of CDX2 and cytokeratins 7 and 20 expression in differentiating colorectal adenocarcinomas from extraintestinal gastrointestinal adenocarcinomas: cytokeratin 7-/20+ phenotype is more specific than CDX2 antibody

Use of novel immunohistochemical markers expressed in colonic adenocarcinoma to distinguish primary ovarian tumors from metastatic colorectal carcinoma.

Proliferation, differentiation, and cell death were studied in small intestinal and colonic epithelia of rats after treatment with methotrexate. Days 1-2 after treatment were characterized by decreased proliferation, increased apoptosis, and decreased numbers and depths of small intestinal crypts in a proximal-to-distal decreasing gradient along the small intestine. The remaining crypt epithelium appeared flattened, except for Paneth cells, in which lysozyme protein and mRNA expression was increased. Regeneration through increased proliferation during days 3-4 coincided with villus atrophy, showing decreased numbers of villus enterocytes and decreased expression of the enterocyte-specific genes sucrase-isomaltase and carbamoyl phosphate synthase I. Remarkably, goblet cells were spared at villus tips and remained functional, displaying Muc2 and trefoil factor 3 expression. On days 8-10, all parameters had returned to normal in the whole small intestine. No methotrexate-induced changes were seen in epithelial morphology, proliferation, apoptosis, Muc2, and TFF3 immunostaining in the colon. The observed small intestinal sparing of Paneth cells and goblet cells following exposure to methotrexate is likely to contribute to epithelial defense during increased vulnerability of the intestinal epithelium.

/pdf/selective-sparing-of-goblet-cells-and-paneth-cells-in-the-21ur6ji5mq.pdf

Selective sparing of goblet cells and Paneth cells in the intestine of methotrexate-treated rats

Fibroblast growth factor 19 (FGF19) is proposed to be a negative feedback regulator of hepatic bile acid (BA) synthesis. We aimed to clarify the distribution of FGF19 expression in human intestine ...

https://www.physiology.org/doi/pdf/10.1152/ajpgi.00398.2012

Potent stimulation of fibroblast growth factor 19 expression in the human ileum by bile acids

HOX genes from paralogous groups 4 and 5 are particularly relevant to the gut neuromusculature development because these genes are expressed at the splanchnic mesoderm surrounding the gut diverticulum, and at the level of the neural tube from where the vagal neural crest cells (NCCs) originate. In this study, we examined the migration and differentiation of NCCs, and investigated the expression patterns of HOXB5 in human embryonic guts. Human embryos of gestational week-4 to -8.5 were studied. Vagal NCCs enter the esophagus, migrate, and colonize the entire gut in a rostrocaudal manner between week-4 and week-7. The migrating NCCs in gut express HOXB5. Two separate and discontinuous mesenchymal expression domains of HOXB5 were detected in the gut: the distal domain preceding the migratory NCCs; and the proximal domain overlapping with the NCCs. The two expression domains shift caudally in parallel with the rostrocaudal migration of NCCs between week-4 and week-5. Neuron and glia differentiation of NCCs are concomitant with HOXB5 down-regulation in NCCs and the mesenchyme. By week-7, myenteric plexuses have formed; HOXB5 expression is switched on in the plexuses. We found that (1) the migratory route of NCCs in human embryonic gut was similar to that in mice and chicks; and (2) the expression pattern of HOXB5 correlated with the migration and differentiation of NCCs, suggesting a regulatory role of HOXB5 in the development of NCCs.

https://anatomypubs.onlinelibrary.wiley.com/doi/pdf/10.1002/dvdy.10350

HOXB5 expression is spatially and temporarily regulated in human embryonic gut during neural crest cell colonization and differentiation of enteric neuroblasts

https://www.gastrojournal.org/article/S0016-5085(97)00371-5/pdf

Differences in expression of homeobox transcription factors in proximal and distal human small intestine

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Differences in expression of homeobox transcription factors in proximal and distal human small intestine