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Colorectal cancer markers

Find the right cancer biomarker for your research using our cancer immunohistochemistry (IHC) guide to colorectal cancer.
Last edited Thu 06 Jul 2023

Here we look at some of the most common primary IHC markers for colorectal cancer (CRC) and cell type-specific biomarkers. We also recommend specific antibodies for each biomarker for use in key applications such as IHC.

NOTUM

NOTUM is a key mediator during the early stages of mutation fixation that can be targeted to restore wild-type cell competitiveness and provide preventative strategies for people at a high risk of developing colorectal cancer.

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References

View 1 reference for NOTUM

Calretinin

Calretinin is a calcium-binding protein that plays a role in message targeting and intracellular calcium buffering. While absent in normal colonocytes, it is expressed in most poorly differentiated colon carcinomas. Strongly positive calretinin staining in colon medullary carcinoma, as well as correlations between the expression of calretinin and the degree of differentiation in human colorectal adenocarcinomas, have been reported emphasizing the potential of calretinin as an IHC biomarker for bowel cancer.

IHC stain (marker localization): Cytoplasmic and nuclear  

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Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) analysis of human mesothelioma tissue sections labeling calretinin with purified ab92341 at 1:4000 (0.034 µg/mL).

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References

View 3 references for Calretinin

MUC2

MUC2 is part of the mucin family and characteristically observed in goblet cells of small and large bowel mucosa. It is involved with coating the epithelia of the intestines, airways, and other mucus membrane-containing organs. Loss of MUC2 expression has been reported to be a predictor of adverse outcomes, and further prospective studies that evaluate adjuvant chemotherapy in stages II and III of colon cancer should include MUC2 expression analysis for patient stratification.

IHC stain (marker localization): Intestine, secreted into the inner and outer mucus layers 

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Immunohistochemical analysis of paraffin-embedded human colonic adenocarcinoma tissue using unpurified ab134119 showing +ve staining.

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References

View 1 reference for MUC2

COX-2

COX-2 is an inducible enzyme that regulates prostaglandin synthesis and is overexpressed in several epithelial cancers. It is involved in the regulation of apoptosis, angiogenesis, and tumor cell invasiveness which contribute to its effects on tumorigenesis. Multiple studies have shown that selective COX-2 inhibitors are a great targeted approach to the chemoprevention of CRC.

IHC stain (marker localization): Microsome membrane and endoplasmic reticulum

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Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) analysis of human colonic carcinoma tissue labeling COX2 / Cyclooxygenase 2 with unpurified ab179800 at a dilution of 1/250.

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References

View 2 references for COX-2

LI Cadherin

LI Cadherin is one of a group of cadherins that act as calcium-dependent cell adhesion proteins that preferentially interact with themselves in a homophilic manner in connecting cells. High LI Cadherin expression has been associated with liver metastasis, a major cause of death associated with colorectal cancer, and poor survival of patients.

IHC stain (marker localization): Cell membrane

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References

View 1 reference for LI Cadherin

GPA33

The GPA33 gene codes for A33 antigen, a transmembrane glycoprotein that is expressed in normal colonic and small bowel epithelium as well as more than 95% of human colon cancers. IHC in CRC tissue has shown strong A33 membrane staining in samples of well-differentiated tumors, and there are also proposals for using antibodies to GPA33 as a potentially potent radioimmunotherapy regimen for GPA-33 positive CRC tumors in humans.

IHC stain (marker localization): Cell membrane

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References

View 3 references for GPA33

EGFR

Epidermal growth factor receptor (EGFR) is usually involved in cell growth and is recognized as an important player in CRC initiation and progression. In late-stage colorectal cancer, the most commonly used targeted therapies are monoclonal antibodies that prevent EGFR activation. However, future development of anti-EGFR directed nanoparticles that could inhibit overactive EGFR signals could potentially reduce CRC risk.

IHC stain (marker localization): Secreted and cell membrane

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Formalin-fixed, paraffin-embedded human colon adenocarcinoma tissue stained for EGFR using ab227642 at 1/100 dilution in immunohistochemical analysis.

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References

View 3 references for EGFR

VEGF

VEGF is a heparin-binding glycoprotein with potent angiogenic activity within endothelial cells. Angiogenesis is crucial for the progression of colorectal carcinoma. VEGF is expressed in around 50% of colorectal cancers and shows very low expression in normal colonic mucosa, making it a good biomarker for the diagnosis of CRC from histology samples.

IHC stain (marker localization): Secreted protein 

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Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) analysis of human kidney tissue sections labeling VEGFA with purified ab52917 at 1:100 dilution (2.96 µg/mL).

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References

View 1 reference for VEGF

p53

The tumor suppressor p53 is a transcription factor involved in cell cycle arrest and apoptosis under cellular stress. Mutations within p53 are one of the most frequent triggers leading to the progression of CRC and are found in 34% of the proximal colon tumors and 45% of distal colorectal tumors.

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Formalin-fixed, paraffin-embedded human colon carcinoma tissue stained for p53 using ab16665 at 1/100 dilution in immunohistochemical analysis.

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Ki67

Ki67 is an important protein involved in cell division and is commonly used as a marker of cellular proliferation. Quantifying Ki67 expression by IHC will give you the Ki67 labeling index, which is commonly used in clinical pathology to estimate cancer prognosis. High Ki67 expression is thought to be an indication of a good prognosis for patients with colorectal cancer. 

IHC stain (marker localization): Nuclear

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ab15580 staining Ki67 proliferation marker in human colon tissue sections by IHC-P (formaldehyde-fixed paraffin-embedded sections).

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Insulin-like growth factor binding protein 2 (IGFBP2)

IGFBP-2 interacts with the extracellular matrix, proteoglycans, and integrin receptors within many different cell types. It may also act as a transcription factor to stimulate gene expression. Studies have shown that IGFBP-2 is uniquely distributed at the bottom of human colonic crypts and that increased levels of IGFBP-2 can be seen in many colorectal cancers.  This expression co-localizes with the phosphorylated p65 subunit of NF-kB, making these good biomarkers for CRC.

IHC stain (marker localization): Secreted protein

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References

View 1 reference for Insulin-like growth factor binding protein 2 (IGFBP2)

PKM2

The M2 isoform of PK (PKM2) is a glycolytic enzyme involved in aerobic glycolysis and anabolic metabolism in cancer cells. PKM2 also promotes the transcription of Oct-46, HIF-1α7, STAT38, and β-catenin during the progression of various cancers.

IHC stain (marker localization): Nuclear and cytoplasm 

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Immunohistochemical analysis of paraffin-embedded human cervical carcinoma, labeling PKM using ab154816 at 1/100 dilution.

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CDX2

CDX2 is a transcription factor expressed specifically in the intestine, where it is involved in the maintenance of intestinal cell types. Low CDX2 expression in CRC is associated with advanced stages of cancer progression, vessel invasion, and metastasis. Over 20% of CRC show some reduction of CDX2 protein by histology. Seeing normal or high levels of CDX2 expression is a biomarker for a good prognosis for survival from the disease.

IHC stain (marker localization): Nuclear 

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Unpurified ab76541 showing positive staining in colonic adenocarcinoma tissue. Heat-mediated antigen retrieval was performed before commencing with IHC staining protocol.

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References

View 1 reference for CDX2

Ep-CAM

Ep-CAM is a common biomarker used in colorectal adenocarcinoma to discriminate cancer cells from mesothelial cells. Being able to distinguish between adenocarcinoma and mesothelial cells by histology is crucial for clinicians to be able to correctly diagnose and assign treatment to patients. 

IHC stain (marker localization): Cell membrane

View antibodies to Ep-CAM

Immunohistochemical analysis of paraffin-embedded human colon tissue labeling EpCAM with ab223582 at 1/500 dilution, followed by goat anti-rabbit IgG H&L (HRP) Ready to use. Membranous staining on human colon is observed (PMID: 15637741). Counterstained with hematoxylin.

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Villin

Villin is an actin-binding protein expressed in the epithelial cells lining the gut and has been shown to regulate epithelial-mesenchymal transition (EMT) in colorectal cancers. Microsatellite instability (MSI) colorectal cancers have also been shown to have very low levels of Villin expression compared to normal gut epithelial cells. This loss of Villin leads to poorly differentiated histology of the CRC.

IHC stain (marker localization): Cytoplasm

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Immunohistochemical analysis of paraffin-embedded human colon adenocarcinoma tissue labeling villin with ab133510 at 1/100 dilution.

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References

View 1 reference for Villin

CK7 (Cytokeratin 7) and CK20 (Cytokeratin 20)

CK7 and CK20 are cytokeratins expressed in the gut epithelia. Different CK7 and CK20 IHC expression patterns are commonly used to distinguish colorectal adenocarcinomas. Most colorectal cancers are CK7 negative and CK20 positive, making the combination of these cytokeratins an excellent biomarker combination. CK7 and CK20 expression varies between colorectal carcinomas according to histological grade and tumor location. 

IHC stain (marker localization) for CK7 and CK20: Cytoplasm

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View antibodies to CK20

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References

View 1 reference for CK7 (Cytokeratin 7) and CK20 (Cytokeratin 20)

References

CK7 (Cytokeratin 7) and CK20 (Cytokeratin 20)

Chu, P.,, Wu, E.,, Weiss, L. M. Cytokeratin 7 and Cytokeratin 20 expression in epithelial neoplasms: A survey of 435 cases. Modern Pathology 13 (9),962–972 (2000)