Tenth Issue of “Mai Mai” Pathology Weekly Reading Notes | Immunohistochemical Markers for Gastrointestinal Tumors (Part 1): Epithelial Tumors

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6 2 月, 2026

On 6 2 月, 2026

Preface:

Gastrointestinalspecimens occupy a significant portion of the daily work of pathologists. Undoubtedly, immunohistochemistry plays a very important role in their diagnosis and differential diagnosis. To facilitate a more systematic and comprehensive understanding for fellow pathologistsof the knowledge regarding commonly used immunohistochemical markers for gastrointestinal tumors,we will introduce them in two parts: epithelial tumors and mesenchymal tumors.

Immunohistochemical Markers for Gastrointestinal Tumors: Epithelial Tumors

Table 1. Overview of Immunohistochemical Indicators for Gastrointestinal Epithelial Tumors

(Click to view larger image)

Remarks

The medullary type in adenocarcinoma is generally negative;
Nuclear staining;
Well-differentiated neuroendocrine tumor (carcinoid);
Well-differentiated neuroendocrine carcinoma (atypical carcinoid);
Poorly differentiated neuroendocrine carcinoma;
Enterochromaffin-like cells.

Detailed Explanation of Indicators

CDX-2

CDX-2 is a transcription factor protein that regulates the differentiation and proliferation of intestinal epithelium. Normally, CDX-2 expression begins in the late stages of gastrointestinal embryonic development and is present in the mucosa distal to the stomach, thus it can be expressed in various cell types of adult intestinal mucosa, such as absorptive epithelium, goblet cells, Paneth cells, and neuroendocrine cells. CDX-2 is also an early marker for Barrett’s metaplasia of the esophagus, and its expression indicates the transformation of squamous epithelium into columnar epithelium with goblet cells.

CDX-2 can be expressed in adenocarcinomas of the esophagus and gastrointestinal tract, as well as in neuroendocrine tumors from different intestinal regions. The highest positive rate and intensity are seen in colorectal adenocarcinoma. Expression of CDX-2 is generally accompanied by CK20 expression.

Figure 1. Metastatic colorectal adenocarcinoma, with strong nuclear positive expression of CDX-2 in tumor cells.

Positive expression pattern: Nuclear

Recommended positive control tissue: Appendix

CDX-2 expression can also be found in many non-gastrointestinal adenocarcinomas: it shows high expression levels in bladder adenocarcinoma of urachal origin, pancreatic cancer, biliary adenocarcinoma, and ovarian mucinous carcinoma. There are also reports of CDX-2 expression in individual prostate cancers. Lung adenocarcinomas with mucinous differentiation can also express CDX-2, and this type of lung adenocarcinoma also expresses CK20 but does not express TTF-1. Some neuroendocrine tumors outside the gastrointestinal tract may also express CDX-2. Conversely, anaplastic high-grade gastrointestinal adenocarcinomas and medullary carcinoma within adenocarcinomas may show loss of CDX-2 expression.

SATB2

SATB2 is also a transcription factor and a DNA-binding protein involved in osteoblast differentiation, making it an important diagnostic marker for osteosarcoma. In the gastrointestinal context, SATB2 is selectively expressed in colorectal epithelium and is not expressed in the mucosa of the stomach, small intestine, or pancreatic epithelium; therefore, this marker is specific for colorectal adenocarcinoma, including medullary carcinoma. In daily practice, SATB2 is generally used in combination with CK20.

Figure 2. Rectal adenocarcinoma with lung metastasis, showing strong nuclear positive expression of SATB-2 in tumor cells.

Positive expression pattern: Nuclear

Recommended positive control tissue: Appendix

SATB2 can also be selectively expressed in neuroendocrine tumors of the left colon and rectum, while neuroendocrine tumors from other sites are reportedly negative or weakly positive. Low-level expression of SATB2 has also been reported in a few lung adenocarcinomas and ovarian cancers; adenocarcinomas of the upper gastrointestinal tract and pancreas generally do not express it.

CDH17

CDH17 is a member of the calcium-dependent cadherin family and is regulated by CDX-2. Normally, this marker is expressed in gastrointestinal and pancreatic epithelial cells and related adenocarcinomas, while lung adenocarcinoma, breast cancer, papillary thyroid carcinoma, transitional cell carcinoma, renal cell carcinoma, hepatocellular carcinoma, and mesothelioma are generally negative.

Figure 3. Positive CDH17 in gastric adenocarcinoma.

Positive expression pattern: Cell membrane and cytoplasm

Recommended positive control tissue: Appendix

Villin

Villin is an actin-binding protein and a component of the brush border in various types of epithelium, specifically such as intestinal mucosa, fallopian tube and vas deferens mucosa, and the lining epithelium of proximal renal tubules. Villin is positively expressed in gastrointestinal adenocarcinomas and can also be positive in ovarian cancer, endometrioid carcinoma, and renal cell carcinoma; well-differentiated neuroendocrine tumors from different origins also express it.

Maimai: “CDX2 is an intestine-specific transcription factor expressed early in intestinal development, involved in regulating the proliferation and differentiation of intestinal epithelial cells, thus playing an important role in gastrointestinal epithelial metaplasia and tumorigenesis. Normally, this marker is expressed in the villi and crypt surfaces of intestinal epithelium, from duodenal to rectal epithelial cells. Used in combination with Villin, it can differentiate colorectal adenocarcinoma from metastatic adenocarcinoma. CDX2 expression is closely related to the occurrence of gastric cancer, detectable in 74% of gastric cancers. It is important to note that loss of CDX2 promotes the development of sporadic colon cancer, as mentioned in this article, medullary carcinoma in colon adenocarcinoma does not express this marker. SATB2 is mainly used for the diagnosis of osteosarcoma and its differential diagnosis from other non-osteogenic sarcomas. Additionally, this marker is highly expressed in colorectal cancer, while other tumors such as pancreatic, gastric, gallbladder, ovarian, cervical, and endometrial adenocarcinomas rarely express it or are negative, thus it can also serve as a sensitive and specific marker for lower gastrointestinal tumors (e.g., colorectal cancer) when used in combination with CK7 and CK20.”

Antibody Name	Clone Number	Positive Control	Positive Location
^CDX-2*	MX024	Appendix, colon adenocarcinoma	Nucleus
CDX-2	EPR2764Y	Appendix, colon adenocarcinoma	Nucleus
^SATB2	EP281	Colon, osteosarcoma	Nucleus
Villin*	MX021	Colonadenocarcinoma, appendix	Cytoplasm
^Villin	CWWB1	Colonadenocarcinoma, appendix	Cytoplasm

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