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Pancreatic cancer biomarkers

Find the right cancer biomarker for your research using our IHC guide to pancreatic cancer.
Last edited Mon 29 Apr 2024

Download the complete Cancer biomarkers guide here.

Pancreatic cancer is the 7th leading cause of cancer-related death worldwide, with a higher death toll in developed countries. The most common subtype of pancreatic cancer is pancreatic ductal adenocarcinoma, accounting for approximately 85% of all cases. Globally, the mortality rate coincides with the incidence rate, emphasizing the poor prognosis for this cancer type1. Immunohistochemistry offers a useful assay in the identification and classification of pancreatic neoplasms.

The diagnostic accuracy for this cancer type has been significantly improved by the continuous discovery and validation of new tumor-associated biomarkers and the development of effective immunohistochemical panels. The application of appropriate IHC panels allows pathologists to differentiate between the different types of pancreatic cancer and to distinguish pancreatic carcinomas from other secondary metastatic cancers.

TFF3

Alternative names:

Trefoil factor 3

Gene names:

TFF3

TFF3 has been used for the detection of pancreatic ductal adenocarcinoma in urine samples.

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References

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PTX3

Alternative names:

Pentraxin-related protein PTX3, pentraxin 3, TNF-inducible gene 14, TSG-14

Gene names:

PTX3

PTX3 is a stromal compartment-specific pancreatic cancer biomarker that is suitable for validation studies.

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References

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IMP3

Alternative names:

Insulin-like growth factor II mRNA-binding protein 3, IGF2BP3, KOC

Gene names:

IGF2BP3

IMP3, a cell-surface glycoprotein, is not expressed in the normal pancreatic ductal epithelium and so may serve as a sensitive and specific biomarker to discriminate between benign and malignant pancreatic epithelium. This biomarker may play a role in the migration, invasion, and adhesion of pancreatic cell cancer. Identification of IMP3 by IHC is associated with poor prognosis of pancreatic ductal adenocarcinoma. 

IHC stain: Nuclear and cytoplasmic

Figure: Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) analysis of human lung cancer tissue sections labeling IMP3 with purified ab179807 at 1/1000 dilution (0.10 µg/mL). IHC stain: Nuclear and cytoplasmic Recommended IHC antibody: ​Recombinant Anti-IMP3 anitbody [ERP12021-114] (ab179807)

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References

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S100P

Alternative names:

S100 calcium-binding protein P

Gene names:

S100P

S100P is a sensitive and specific diagnostic biomarker for pancreatic cancer. It has a potential role in the proliferation, survival, motility, and invasiveness of pancreatic cells. Levels of S100P expression increase during the progression from pancreatic intraepithelial neoplasia to invasive adenocarcinoma. This biomarker can be used to differentiate between positive pancreatic adenocarcinoma and negative pancreatic endocrine tumors.

IHC stain: Nuclear and cytoplasmic

Figure: Formalin-fixed paraffin-embedded human pancreatic adenocarcinoma tissue labeled with Anti-S100P (ab133554) at 1:250 in IHC.

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References

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MUC1

Alternative names:

Epithelial Membrane Antigen, EMA, CD227, episialin, polymorphic epithelial mucin, Mucin short variant S1

Gene names:

MUC1

In normal cells, MUC1 acts as a barrier to the apical surface of epithelial cells, playing a protective and regulatory role. In pancreatic adenocarcinoma, MUC1 is highly expressed and associated with poor patient prognosis.

IHC stain: Membranous and cytoplasmic

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References

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Mesothelin

Alternative names:

MSLN

Gene names:

MSLN

Mesothelin is expressed on the surface of pancreatic adenocarcinoma cells and may play a role in cell adhesion. It serves as a diagnostic and prognostic biomarker for pancreatic cancer and may be used to target immunotherapy. Mesothelin expression in pancreatic adenocarcinoma is associated with high tumor aggressiveness and poor patient outcomes.

IHC stain: Extracellular, cell membrane and punctate cytoplasmic staining

Figure: Formalin-fixed paraffin-embedded human pancreatic carcinoma labeled with Anti-Mesothelin (ab134109) using unpurified antibody in IHC analysis.

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References

View 1 reference for Mesothelin

SMAD4

Alternative names:

Mothers against decapentaplegic homolog 4,, DPC4, deleted in Pancreatic Cancer-4

Gene names:

SMAD4

Also known as DPC4 and MADH4. SMAD4 acts downstream of TGF-β as a tumor suppressor by inhibiting growth and promoting apoptosis. Loss of function of SMAD4 may, therefore, act as a tumorigenic factor. Loss of SMAD4 expression in IHC has been associated with poor survival and may represent a negative prognostic biomarker in patients with pancreatic cancer.

IHC stain: Nuclear staining in normal cells with loss of nuclear staining in malignancy

Figure: Formalin-fixed paraffin-embedded human pancreatic adenocarcinoma labeled with Anti-SMAD4 (ab217267) at 1:100 in IHC.

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References

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TOP2A

Alternative names:

DNA topoisomerase IIα

Gene names:

TOP2A

Toposiomerase II alpha (TOP2A)

TOP2A cleaves the double-stranded DNA helix in protein synthesis and DNA replication. Overexpression of this enzyme induces tumor development and progression11. TOP2A overexpression is correlated with tumor metastasis and shorter patient survival times; thus, TOP2A is considered a prognostic biomarker in pancreatic cancer. 

IHC stain: Cytoplasmic and nuceloplasmic

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References

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CEACAM1

Alternative names:

Carcinoembryonic antigen-related cell adhesion molecule 1, biliary glycoprotein, Cluster of Differentiation 66a, CD66a

Gene names:

CEACAM1

Also called CD66, biliary glycoprotein, BGP and C-CAM.  CEACAM1 is a cell adhesion molecule expressed in adenocarcinomas and in pancreatic intraductal neoplasia lesions. Initially regarded as a tumor suppressor as its expression shows considerable downregulation within the epithelia in the early phases of solid cancers, more recently CEACAM1 has been suggested as a biomarker for the progression of malignancy and metastatic spread. 

IHC stain: Secreted and cell membranous

Figure: Immunohistochemical analysis of paraffin-embedded human hepatic carcinoma tissue labeling CEACAM1 with ab300061 at 1/2000 followed by a ready-to-use LeicaDS9800 (BOND™ Polymer Refine Detection). Positive staining on human hepatic carcinoma (PMID: 27377843). IHC stain: Secreted and cell membranous Recommended IHC antibody: ​Recombinant Anti-CEACAM1 antibody[EPR4049] (ab108397)

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References

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Thymidylate synthase

Gene names:

TYMS

Under normal conditions, this enzyme contributes to the de novo mitochondrial thymidylate biosynthesis pathway. It is the target for 5-fluorouracil (5-FU) in the treatment of pancreatic cancer. Thymidylate synthase has been identified as a prognostic biomarker for favorable outcomes following resection in patients with pancreatic adenocarcinoma.

IHC stain: Cytoplasmic

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References

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REG3A

Alternative names:

Regenerating islet-derived protein 3 alpha, regenerating islet-derived protein III-alpha, hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein, HIP/PAP, peptide 23

Gene names:

REG3A

This pancreatic protein is a calcium-dependent protein that promotes islet growth in response to inflammation or injury. REG3A is an emerging biomarker for pancreatic cancer development. Its role in pancreatic cancer has been linked to inflammation-related pancreatic cancer development. High REG3A expression levels in IHC are common in the early stages of pancreatic cancer and may act as ancillary diagnostic and prognostic factors for the development of pancreatic ductal adenocarcinoma16

IHC stain: Nuclear

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References

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p-glycoprotein

Alternative names:

permeability glycoprotein, P-gp, Pgp, multidrug resistance protein 1, MDR1, ATP-binding cassette sub-family B member 1, ABCB1, cluster of differentiation 243, CD243

Gene names:

ABCB1

P-glycoprotein acts as an ATP-dependent drug efflux pump to remove drugs and toxins from cells. Pancreatic tumors and ductal adenocarcinomas are both associated with elevated expression levels of p-glycoprotein. Expression levels of this novel pancreatic cancer biomarker correlate with a more favorable patient prognosis. 

IHC stain: Cell membrane

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References

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KRAS

Alternative names:

K-Ras, Kirsten rat sarcoma virus

Gene names:

KRAS

This G-protein acts downstream of the epidermal growth factor receptor, and a single amino acid substitution results in an activating mutation.  In pancreatic cancer, KRAS mutations, such as G12D, occur early during carcinogenesis, are present in 90% of tumors, and are associated with poor prognosis1. These mutations are used to differentiate between metastatic pancreatic cancer and primary tumors in other mucinous tissues. 

IHC stain: Cell membrane

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References

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MUC4

Alternative names:

Mucin-4

Gene names:

MUC4

This transmembrane mucin protein functions to provide a protective layer of mucus to the apical surface of epithelial cells. MUC4 is expressed in pancreatic ductal adenocarcinoma but not in normal pancreatic tissue. In pancreatic cancer, it has a proposed role in cancer progression and metastasis.

IHC stain: Secreted and cell membrane

Figure: Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) analysis of human pancreatic carcinoma tissue sections labeling MUC4 with ab183320 at 1/100 dilution (0.49 µg/mL). IHC stain: Secreted and cell membrane Recommended IHC antibody: Recombinant Anti-MUC4 antibody [SP241] - C-terminal (ab183320)

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References

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ERCC1

Alternative names:

Excision repair cross-complementation group 1, 

Gene names:

ERCC1

ERCC1 is an emerging biomarker used in guiding the treatment of pancreatic cancer. It functions in DNA repair, thus playing a role in the resistance to radiation and platinum-based therapies. IHC localization of ERCC1 has, in some cases, been associated with a positive response to chemotherapeutic agents for the treatment of pancreatic cancer.

IHC stain: Nuclear

Figure: Formalin-fixed, paraffin-embedded human lung carcinoma tissue stained for ERCC1 with ab129267 (1/100 dilution) in immunohistochemical analysis. IHC stain: Nuclear Recommended IHC antibody: Recombinant Anti-ERCC1 antibody [EPR7277] (ab129267)

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References

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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

View antibodies to EGFR

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

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Topoisomerase I

Alternative names:

DNA topoisomerase 1

Gene names:

TOPI

This enzyme is essential for genomic stability, acting to remove DNA supercoils. Topoisomerase I has been targeted by many inhibitors as a therapeutic strategy in the treatment of pancreatic cancer. Overexpression of Topoisomerase I is found in approximately half of all pancreatic cancers. It has been used as an IHC biomarker in many clinical studies to monitor patient response to pancreatic cancer therapies and as an emerging biomarker in monitoring the development of this cancer. 

IHC stain: Nuclear

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References

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RRM1

Alternative names:

Ribonucleoside-diphosphate reductase large subunit

Gene names:

RRM1

RRM1 catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides for DNA synthesis. IHC assay of RRM1 in pancreatic cancer has been used to predict patient response to chemotherapy. High expression levels of RRM1 in pancreatic cancer may serve as a favorable prognostic biomarker. 

IHC stain: Cytoplasmic

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References

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Claudin 4

Alternative names:

CLDN4

Gene names:

CLDN4

Claudin 4 is overexpressed in the majority of pancreatic carcinomas, both in early-stage lesions and advanced tumors. IHC assay of Claudin 4 offers targeting for novel therapeutics of infiltrating pancreatic cancer. Identification of Claudin 4 in the precursor lesions of pancreatic cancer suggests a potential benefit of IHC assay for Claudin 4 as both early diagnostic and prognostic of pancreatic cancer 

IHC stain: Cell membrane
Recommended IHC antibody: Recombinant Anti-Claudin4 antibody [EPRR17575] (ab210796)

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References

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IgG4

Alternative names:

Immunoglobulin G4

Gene names:

IGHG4

This is the least abundant of the IgG subclasses, representing just 6% of IgG. It is commonly expressed in the pancreaticobiliary region and is used in the diagnosis of pancreatic cancer to distinguish between potential carcinoma and sclerotic pancreatic tissue in cases of autoimmune disorders. 

IHC stain: Cytoplasmic

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References

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FOXA2

Alternative names:

Forkhead box protein A2, hepatocyte nuclear factor 3-beta, HNF-3B

Gene names:

FOXA2

FOXA2 is a winged-helix transcription factor that promotes the differentiation of pancreatic glucagon-producing alpha-cells and the differentiation and maintenance of insulin-producing beta-cell secretory and metabolic pathways. This pancreatic tissue biomarker is expressed in both normal and pancreatic ductal adenocarcinomas and may be used to identify pancreatic tissue and metastatic cancers.

IHC stain: Nuclear

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References

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Carboxypeptidase A1

Gene names:

CPA1 

This pancreatic metalloprotease is expressed in pancreatic juice and acts as a digestive enzyme on aromatic and aliphatic amino acid residues exposed by the action of chymotrypsins and elastases. Mutations in this enzyme are commonly associated with pancreatitis, while over-expression may be linked to pancreatic cancers, allowing diagnostic differentiation via IHC between these two conditions.

IHC stain: Secreted

Figure: Immunohistochemical analysis of paraffin-embedded human pancreas tissue labeling Carboxypeptidase A with ab278044 at 1/4000 (0.135 ug/mL) dilution followed by a ready-to-use LeicaDS9800 (Bond® Polymer Refine Detection). IHC stain: Secreted Recommended IHC antibody: ​Recombinant Anti-Carboxypeptidase A antibody [EPR24384-69] (ab278044)

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References

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Pancreatic triacylglycerol lipase

Alternative names:

Human pancreatic lipase, triacylglycerol acyl hydrolase EC3.1.1.3, pancreatic lipase, steapsin

Gene names:

PNLIP

Pancreatic triacylglycerol lipase is secreted by the pancreas and hydrolyzes triglycerides in the small intestine. This enzyme is essential for the efficient digestion of dietary fats. 

Inhibition of Pancreatic triacylglycerol lipase may prevent high-fat diet-induced obesity in mice and result in weight loss in human patients with obesity. Variants of this protein are commonly used in IHC as a biomarker for pancreatitis and may be used to identify pancreatic tissue.

IHC stain: Secreted

Figure: Immunohistochemical analysis of paraffin-embedded human pancreas tissue labeling Pancreatic Lipase/PTL with ab133556 antibody at a dilution of 1/100. IHC stain: Secreted Recommended IHC antibody: Recombinant Anti-Pancreatic Lipase/PTL antibody [EPR6275] (ab133556)

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References

View 1 reference for Pancreatic triacylglycerol lipase

References

Mesothelin

Inaguma S,, Wang Z,, Lasota J,, et al. Comprehensive immunohistochemical study of mesothelin (MSLN) using different monoclonal antibodies 5B2 and MN-1 in 1562 tumors with evaluation of its prognostic value in malignant pleural mesothelioma Oncotarget 8 (16),26744-26754 (2017)

SMAD4

Shugang X,, Hongfa Y,, Jianpeng L,, et al. Prognostic Value of SMAD4 in Pancreatic Cancer: A Meta-Analysis Transl Oncol 9 (1),1-7 (2016)

ERCC1

Strippoli A,, Rossi S,, Martini M,, et al. ERCC1 expression affects outcome in metastatic pancreatic carcinoma treated with FOLFIRINOX: A single institution analysis Oncotarget 7 (23),35159-68 (2016)

Topoisomerase I

Heestand GM,, Schwaederle M,, Gatalica Z,, et al. Topoisomerase expression and amplification in solid tumours: Analysis of 24,262 patients Eur J Cancer 83 ,80-87 (2017)