Pancreatic cancer is the 7^th 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 type 1. Identifying risk factors and using tumor markers are crucial for early detection and improved outcomes in pancreatic cancer. Immunohistochemistry offers a useful assay in the identification and classification of pancreatic neoplasms.

A physical exam and thorough review of medical history, including family history, are initial steps in the diagnostic process for people with pancreatic cancer. Individuals with a family history of pancreatic cancer or known genetic mutations are at increased risk. They may be considered high risk, making them candidates for genetic testing and specialized screening protocols. Pancreatic cancer involves a combination of imaging tests, certain blood tests (such as those measuring the carbohydrate antigen CA19-9), and lab tests to detect pancreatic cancer, especially in people with early-stage pancreatic cancer or those who suspect pancreatic cancer due to symptoms. A blood sample is collected for tumor marker testing, and other tests and other blood tests may be required to confirm diagnosis or monitor disease progression. If initial findings are abnormal, further tests and more tests, such as advanced imaging or biopsy, are often needed. Developing pancreatic cancer is frequently asymptomatic in early stages, making early detection challenging, and recognizing pancreatic cancer symptoms is important for timely diagnosis.

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. Blood tests, including tumor marker assays, play a significant role in the pancreatic cancer diagnosis process. Early detection is vital, and tumor markers measured through blood tests, such as CA 19-9, are used to help diagnose pancreatic cancer and monitor its progression. 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

Trefoil factor 3 (TFF3) is a small peptide primarily secreted by epithelial cells and known for its role in mucosal healing. Recent studies have shown that TFF3 is overexpressed in pancreatic ductal adenocarcinoma (PDAC), where it may influence tumor progression. TFF3 appears to activate multiple signaling pathways, including WNT, EGFR, and PI3K/AKT, supporting cell proliferation, invasion, and survival. Its expression correlates with poorer patient outcomes, making it a potential biomarker for PDAC. Ongoing research is exploring how TFF3 modulation could support diagnostic and therapeutic strategies in pancreatic cancer.

Figure 1. Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-Trefoil Factor 3 antibody [EPR3974] (ab108599).

Recommended products

PTX3

Pentraxin 3 (PTX3) is a protein involved in innate immunity and inflammation, produced by various cells, including stromal and immune cells. In pancreatic ductal adenocarcinoma (PDAC), PTX3 is secreted by activated pancreatic stellate cells and contributes to tumor progression by organizing the extracellular matrix and supporting cell invasion. Elevated PTX3 levels in serum have been associated with PDAC and may offer diagnostic value beyond traditional markers like CA19-9. Its expression also correlates with inflammatory mediators, suggesting a role in prognosis. PTX3 is under investigation as a stromally-derived biomarker in clinical trials targeting the tumor microenvironment.

Figure 2. Western blot - Anti-Pentraxin 3/PTX3 antibody [EPR6699] (ab125007).

Recommended products

IMP3

IMP3, or insulin-like growth factor II mRNA-binding protein 3, is a cell-surface glycoprotein not expressed in normal pancreatic ductal epithelium. Its selective expression in malignant tissue makes it a promising biomarker for distinguishing pancreatic ductal adenocarcinoma (PDAC) from benign lesions. IMP3 may influence cancer cell migration, invasion, and adhesion, contributing to tumor aggressiveness. Immunohistochemical detection of IMP3 has been linked to poorer clinical outcomes. Studies suggest that combining IMP3 with other markers, such as p53, may improve diagnostic sensitivity in fine-needle aspiration samples, supporting its potential role in early detection and prognosis of PDAC.

Figure 3. Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-IMP3 antibody [EPR12021-114] (ab179807).

Recommended products

S100P

S100P is a highly sensitive and specific diagnostic biomarker for pancreatic cancer, playing a pivotal role in tumor progression and aggressiveness. This calcium-binding protein is significantly overexpressed in pancreatic ductal adenocarcinoma and is involved in key oncogenic processes such as cell proliferation, survival, motility, and invasiveness. S100P expression increases progressively from pancreatic intraepithelial neoplasia (PanIN) to invasive carcinoma, making it a valuable marker for early detection. It also helps differentiate pancreatic adenocarcinoma from pancreatic endocrine tumors. Moreover, S100P interacts with the RAGE receptor, activating pathways like MAPK and NF-κB, which promote tumor growth and metastasis. Its correlation with immune suppression and tumor microenvironment modulation further underscores its potential as a therapeutic target and prognostic indicator.

Figure 4. Flow Cytometry (Intracellular) - Anti-S100P antibody [EPR6143] (ab133554).

Recommended products

MUC1

MUC1 is a membrane-bound glycoprotein commonly overexpressed in pancreatic ductal adenocarcinoma. It plays a role in tumor progression by promoting epithelial to mesenchymal transition, enhancing invasiveness, and metastasis. MUC1 also contributes to chemoresistance by regulating multidrug resistance genes through both Akt-dependent and independent pathways. Its cytoplasmic tail interacts with transcriptional machinery, influencing gene expression linked to tumor survival. These characteristics make MUC1 a widely studied biomarker in pancreatic cancer research and a potential target for therapeutic strategies. Understanding its function may support efforts to improve diagnostic and treatment approaches in oncology.

Figure 5. Immunocytochemistry/ Immunofluorescence - Anti-MUC1 antibody [EPR1023] (ab109185).

Recommended products

Mesothelin

Mesothelin is a glycosylphosphatidylinositol-linked surface protein overexpressed in several cancers, including pancreatic ductal adenocarcinoma. It binds to MUC16, a membrane-associated mucin, enhancing cell motility and invasion through matrix metalloproteinase-7 activation via the p38 MAPK pathway. This interaction is often observed at the invasive front of tumors and is associated with poor patient outcomes. Mesothelin is also shed into the bloodstream, making it a candidate for serum-based biomarker studies. Its role in tumor progression and immune evasion continues to be explored, offering insights into potential diagnostic and therapeutic strategies in pancreatic cancer.

Figure 6. Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-Mesothelin antibody [EPR2685(2)] (ab134109).

Recommended products

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.

Figure 7. Immunocytochemistry/ Immunofluorescence - Anti-Smad4 antibody [SP306] - C-terminal (ab217267).

Recommended products

TOP2A

TOP2A, or DNA topoisomerase II alpha, is an enzyme involved in managing DNA topology during replication and transcription. In pancreatic cancer, TOP2A is frequently overexpressed and linked to increased cell proliferation and genomic instability. Its expression peaks during the G2/M phase of the cell cycle, making it a marker of active cell division. Studies suggest that elevated TOP2A levels may correlate with poor prognosis and resistance to certain chemotherapies. As a result, TOP2A is being explored as a potential biomarker for diagnosis and treatment monitoring in pancreatic cancer.

Figure 8. Western blot - Anti-Topoisomerase II alpha antibody [EP1102Y] (ab52934).

Recommended products

CEACAM1

CEACAM1, or carcinoembryonic antigen-related cell adhesion molecule 1, is a glycoprotein involved in cell adhesion, immune regulation, and signal transduction. In pancreatic cancer, CEACAM1 is often overexpressed and linked to tumor progression, angiogenesis, and immune evasion. It can form homodimers or heterodimers, influencing intracellular signaling pathways that affect cell proliferation and motility. CEACAM1 is also detectable in serum, making it a candidate for non-invasive biomarker studies. Its dynamic expression and functional versatility continue to attract interest in cancer diagnostics and therapeutic development.

Figure 9. Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-CEACAM1 antibody [EPR4049] (ab108397).

Recommended products

Thymidylate synthase

Thymidylate synthase (TS) is a key enzyme in DNA synthesis, catalyzing the conversion of dUMP to dTMP. In pancreatic cancer, TS is often overexpressed and associated with increased cell proliferation and resistance to fluoropyrimidine-based chemotherapy. Elevated TS levels may contribute to tumor progression by supporting rapid DNA replication and repair. Studies using transgenic models have shown that high TS expression in pancreatic tissue can lead to hyperplasia and tumor formation. These findings support ongoing research into TS as a potential biomarker for prognosis and treatment response in pancreatic cancer.

Figure 10. Flow Cytometry (Intracellular) - Anti-Thymidylate Synthase antibody [EPR4545] (ab108995).

Recommended products

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 adenocarcinoma.

Figure 11. Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-REG3A + REG3G antibody [EPRR18188] (ab202057).

Recommended products

p-glycoprotein

P-glycoprotein (P-gp), a membrane-bound transporter encoded by the ABCB1 gene, plays a role in drug efflux and cellular detoxification. In pancreatic cancer, particularly pancreatic ductal adenocarcinoma, P-gp expression has been linked to multidrug resistance and tumor progression. Its presence in tumor tissues may help differentiate malignant from benign pancreatic conditions. Researchers are exploring P-gp as part of glycoprotein biomarker panels to improve diagnostic accuracy and treatment monitoring. While not yet a standard clinical marker, its potential in early detection and therapy response assessment continues to be investigated across proteomic and immunohistochemical studies.

Figure 12. Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-P Glycoprotein antibody [EPR10364-57] (ab170904).

Recommended products

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 prognosis. These mutations are used to differentiate between metastatic pancreatic cancer and primary tumors in other mucinous tissues.

Figure 13. Multiplex immunohistochemistry - Anti-Ras antibody [EPR23474-20] (ab275875).

Recommended products

MUC4

MUC4 is a high molecular weight transmembrane glycoprotein found in various epithelial tissues. In pancreatic cancer, MUC4 is frequently overexpressed and has been linked to increased tumor cell growth, motility, and resistance to apoptosis. It interacts with signaling pathways such as HER2/ERK, influencing cell survival and chemoresistance. MUC4 expression often appears early in pancreatic intraepithelial neoplasia, making it a potential biomarker for early detection and disease progression. Its role in modulating the tumor microenvironment continues to be explored, offering insights into pancreatic cancer biology and potential therapeutic strategies.

Figure 14. Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-MUC4 antibody [SP241] - C-terminal (ab183320).

Recommended products

ERCC1

ERCC1 (excision repair cross-complementation group 1) is a DNA repair protein involved in the nucleotide excision repair pathway. ERCC1 is an emerging biomarker used to guide the treatment of pancreatic cancer. It functions in DNA repair, thus playing a role in the resistance to radiation and platinum-based therapies. ERCC1 expression can influence the effectiveness of radiation therapy and targeted therapy in pancreatic cancer treatment. Understanding ERCC1 status can help guide personalized cancer treatment decisions, including selecting appropriate cancer treatment options such as surgery, chemotherapy, radiation therapy, and targeted therapy. IHC localization of ERCC1 has, in some cases, been associated with a positive response to chemotherapeutic agents for treating pancreatic cancer.

Figure 15. Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-ERCC1 antibody [EPR7277] (ab129267).

Recommended products

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.

Figure 16. Immunocytochemistry/ Immunofluorescence - Anti-EGFR antibody [E234] (ab32198).

Recommended products

Topoisomerase I

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.

Figure 17. Immunocytochemistry/ Immunofluorescence - Anti-Topoisomerase I antibody [EPR5375] (ab109374).

Recommended products

RRM1

RRM1 (ribonucleotide reductase regulatory subunit M1) is a key enzyme in DNA synthesis, converting ribonucleotides into deoxyribonucleotides. In pancreatic cancer, RRM1 expression has been linked to tumor progression and response to chemotherapy. Elevated RRM1 levels may reduce sensitivity to gemcitabine, a common treatment, by maintaining DNA replication under stress. Recent studies also suggest that RRM1 influences DNA repair and genomic stability. Its expression, particularly when assessed alongside ERCC1, may help predict patient outcomes and guide treatment strategies. Ongoing research continues to explore how RRM1 modulation could support more personalized approaches in pancreatic cancer care.

Figure 18. Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-RRM1 antibody [EPR8483] (ab137114).

Recommended products

Claudin 4

Claudin 4 is a tight junction protein that helps regulate cell-to-cell adhesion and barrier function in epithelial tissues. In pancreatic cancer, particularly pancreatic ductal adenocarcinoma, Claudin 4 is frequently overexpressed. This elevated expression has been observed in both cancer cell lines and high-grade intraductal papillary mucinous neoplasms. Its presence may reflect neoplastic progression and has been linked to specific histological subtypes. Claudin 4 is being investigated as a biomarker for early detection and stratification of pancreatic lesions. Its role in tumor biology continues to be explored, offering potential insights into diagnosis and therapeutic targeting.

Figure 19. Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-Claudin 4 antibody [EPRR17575] (ab210796).

Recommended products

IgG4

IgG4 is a subclass of immunoglobulin G known for its anti-inflammatory properties and involvement in immune regulation. In pancreatic cancer, elevated IgG4 levels have been observed in some patients, particularly those with autoimmune pancreatitis, a condition that can mimic malignancy. This overlap has prompted interest in IgG4 as a potential biomarker for differential diagnosis. Additionally, immune evasion through class-switching to IgG4 has been reported in pancreatic tumors, suggesting a role in tumor progression. While not yet widely adopted in clinical oncology, IgG4 continues to be studied for its diagnostic and immunological relevance in pancreatic cancer.

Figure 20. Western blot - Anti-IgG4 antibody [EP4420] (ab109493).

Recommended products

FOXA2

FOXA2 (forkhead box A2) is a transcription factor involved in regulating gene expression during organ development, including the pancreas. It plays a role in chromatin remodeling and helps establish pancreatic cell identity. In pancreatic cancer, FOXA2 expression patterns have been linked to tumor differentiation and progression. It may influence metabolism, cell proliferation, and drug resistance pathways. FOXA2 also interacts with epigenetic regulators, suggesting a broader role in tumor biology. While still under investigation, FOXA2 is gaining attention as a potential biomarker for understanding pancreatic cancer development and guiding future therapeutic strategies.

Figure 21. Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-FOXA2 antibody [EPR4466] (ab108422).

Recommended products

Carboxypeptidase A1

Carboxypeptidase A1 (CPA1) is a digestive enzyme produced by pancreatic acinar cells, primarily involved in protein breakdown. In pancreatic cancer, particularly pancreatic ductal adenocarcinoma, CPA1 expression may be altered due to changes in acinar-to-ductal metaplasia and tumor differentiation. While CPA1 is not widely used as a standalone biomarker, its expression patterns can support histological classification and help distinguish pancreatic cancer from other gastrointestinal tumors. Research continues to explore CPA1’s diagnostic value, especially in combination with other markers, to improve early detection and better understand the molecular changes associated with pancreatic tumor development.

Figure 22. Multiplex immunohistochemistry - Anti-Carboxypeptidase A antibody [EPR24384-69] (ab278044).

Recommended products

Pancreatic triacylglycerol lipase

Pancreatic triacylglycerol lipase is a digestive enzyme responsible for breaking down dietary fats in the small intestine. It is secreted by pancreatic acinar cells and plays a role in lipid metabolism. In pancreatic cancer, particularly during early disease stages, elevated levels of this enzyme have been observed in serum samples. Its increased abundance may reflect changes in pancreatic tissue architecture and enzyme secretion patterns. While not yet widely used in clinical diagnostics, pancreatic triacylglycerol lipase is being investigated as part of biomarker panels aimed at improving early detection and distinguishing malignant from benign pancreatic conditions.

Figure 23. Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-Pancreatic Lipase/PTL antibody [EPR6275] (ab133556).

Recommended products

References

1. Debernardi, S.  et al.  A combination of urinary biomarker panel and PancRISK score for earlier detection of pancreatic cancer: A case-control study.  PLoS Med.  17, e1003489 (2020).

2. Watt, J.  et al.  Role of PTX3 in pancreatic cancer.  Lancet  383, S106 (2014).

3. Han, L. & Patel, C. Utility of IMP3 immunohistochemistry in the distinction of pancreatic adenocarcinoma and chronic pancreatitis.  Am. J. Clin. Pathol.  142, A263 (2014).

4. Pasiliao, C.C.  et al.  The involvement of insulin-like growth factor 2 binding protein 3 (IMP3) in pancreatic cancer cell migration, invasion, and adhesion.  BMC Cancer  15, 266 (2015).

5. Hu, H.  et al.  Diagnostic value of S100P for pancreatic cancer: a meta-analysis.  Tumour Biol.  35, 9479–9485 (2014).

6. Nath, S.  et al.  MUC1 induces drug resistance in pancreatic cancer cells via upregulation of multidrug resistance genes.  Oncogenesis  2, e51 (2013).

7. Inaguma, S.  et al.  Comprehensive immunohistochemical study of mesothelin (MSLN) using different monoclonal antibodies in 1562 tumors.  Oncotarget  8, 26744–26754 (2017).

8. Shugang, X.  et al.  Prognostic value of SMAD4 in pancreatic cancer: A meta-analysis.  Transl. Oncol.  9, 1–7 (2016).

9. Zhou, T.  et al.  Over-expression of TOP2A as a prognostic biomarker in patients with glioma.  Int. J. Clin. Exp. Pathol.  11, 1228–1237 (2018).

10. Simeone, D.M.  et al.  CEACAM1, a novel serum biomarker for pancreatic cancer.  Pancreas  34, 436–443 (2007).

11. Calinescu, A.  et al.  On the dual role of CEACAM1 in human malignancies.  J. Immunol. Res.  2018, 7169081 (2018).

12. Guo, Y.M., Zhu, M. & Yu, W.W. Prognostic significance of thymidylate synthase expression in pancreatic adenocarcinoma: A meta-analysis.  Mol. Clin. Oncol.  3, 121–124 (2014).

13. Liu, X.  et al.  REG3A accelerates pancreatic cancer cell growth under IL-6-associated inflammatory condition.  Biochim. Biophys. Acta  362, 45–60 (2015).

14. Suwa, H.  et al.  Immunohistochemical localization of P-glycoprotein and expression of the MDR1 gene in human pancreatic cancer.  Jpn. J. Cancer Res.  87, 641–649 (1996).

15. Lee, J.  et al.  Impact of EGFR kinase mutations, EGFR gene amplifications, and KRAS mutations on survival of pancreatic adenocarcinoma.  Cancer  109, 1561–1569 (2007).

16. Ansari, D.  et al.  Comparison of MUC4 expression in primary pancreatic cancer and paired lymph node metastases.  Scand. J. Gastroenterol.  48, 1183–1187 (2013).

17. Strippoli, A.  et al.  ERCC1 expression affects outcome in metastatic pancreatic carcinoma treated with FOLFIRINOX.  Oncotarget  7, 35159–35168 (2016).

18. Markman, B.  et al.  EGFR and KRAS in colorectal cancer.  Adv. Clin. Chem.  51, 71–119 (2010).

19. Bertotti, A.  et al.  The genomic landscape of response to EGFR blockade in colorectal cancer.  Nature  526, 263–267 (2015).

20. Pabla, B., Bissonnette, M. & Konda, V.J. Colon cancer and the epidermal growth factor receptor.  World J. Clin. Oncol.  6, 133–141 (2015).

21. Heestand, G.M.  et al.  Topoisomerase expression and amplification in solid tumours: Analysis of 24,262 patients.  Eur. J. Cancer  83, 80–87 (2017).

22. Aoyama, T.  et al.  Clinical implications of RRM1 in pancreatic cancer treated with adjuvant gemcitabine.  Oncol. Lett.  13, 3423–3430 (2017).

23. Thomas, H.  et al.  ERCC1 and RRM1 as predictors of survival in pancreatic ductal adenocarcinoma.  Jefferson Digital Commons  (2011).

24. Kojima, T., Kyuno, D. & Sawada, N. Targeting claudin-4 in human pancreatic cancer.  Expert Opin. Ther. Targets  16, 881–887 (2012).

25. Hamano, H.  et al.  High serum IgG4 concentrations in patients with sclerosing pancreatitis.  N. Engl. J. Med.  344, 732–738 (2001).

26. Sangha Brar, J.S.  et al.  The pancreatic and extrapancreatic manifestations of IgG4-related disease.  Diagn. Interv. Radiol.  24, 83–88 (2018).

27. Gao, N.  et al.  Foxa1 and Foxa2 maintain the metabolic and secretory features of the mature beta-cell.  Mol. Endocrinol.  24, 1594–1604 (2010).

28. Lee, C.S.  et al.  Foxa2 is required for the differentiation of pancreatic alpha-cells.  Dev. Biol.  278, 484–495 (2005).

29. Milan, M.  et al.  FOXA2 controls the cis-regulatory networks of pancreatic cancer cells in a differentiation grade-specific manner.  EMBO J.  38, e101093 (2019).

30. Witt, H.  et al.  Variants in CPA1 are strongly associated with early onset chronic pancreatitis.  Nat. Genet.  45, 1216–1220 (2013).

31. Lasher, D.  et al.  Protease-sensitive pancreatic lipase variants are associated with early onset chronic pancreatitis.  Am. J. Gastroenterol.  114, 974–983 (2019).