Prostate cancer biomarkers

Find the right cancer biomarker for your research using our cancer immunohistochemistry (IHC) guide to prostate cancer.

Prostate cancer is the second most common cancer in men worldwide. IHC is used for diagnosis from prostate biopsy, though the precision and accuracy of the current biomarkers used in this test remain controversial. Therefore, many are looking for alternative specific and sensitive prostate cancer biomarkers to improve outcomes.

While a panel of IHC prostate cancer biomarkers is commonly used for prostate cancer diagnosis (including PSA, AMACR, and high molecular weight cytokeratins), issues around benign tumors mimicking this profile and the early detection of presence and progression of prostate cancer and recurrence following clinical intervention are still not accurately validated by current biomarkers for prostate cancer.

There remains a lack of reliable biomarkers to predict low-risk cancer and avoid overtreatment accurately. As such, aggressive forms of prostate cancer may be missed, and indolent disease may be subjected to unnecessary radical therapy. New biomarker discovery and validation promise to improve early detection and prognosis and provide therapeutic intervention targets.

Prostate specific antigen

Alternative names PSA

PSA is the most widely known biomarker for prostate cancer. It is expressed in prostate epithelial cells and secreted to the seminal fluid, where it’s responsible for cleaving semenogelins. PSA is considered to be a highly sensitive and specific biomarker for prostate tumors. It was approved by the FDA for the diagnosis of prostate cancer in conjunction with the digital rectal exam in 1994. Consequently, the detection of PSA in additional tissues via IHC is typically associated with metastatic cancer of prostatic origin, and the presence of this biomarker is often used to differentiate between prostatic and urothelial carcinomas.

Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) analysis of human prostate cancer tissue sections labeling PSA with purified ab76113 at 1/1000 dilution (0.51 µg/mL).

Figure: Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) analysis of human prostate cancer tissue sections labeling PSA with purified ab76113 at 1/1000 dilution (0.51 µg/mL).

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References

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Alpha-methylacyl-CoA racemase

Alternative names AMACR

AMACR is a mitochondrial and peroxisomal enzyme that functions to oxidize fatty acids and bile acid intermediates. It is over-expressed in the epithelium of approximately 80% of prostate cancer cases and acts as a robust biomarker of prostate cancer. Detection of AMACR via IHC has been shown to be important in the differential diagnosis of prostate carcinoma from benign prostate mimics. AMACR overexpression in prostate cells is indicative of poor patient prognosis, associated with a high Gleason’s score, high initial PSA levels, and indicative of an increased chance of bone metastasis.

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References

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SLC45A3

Alternative names Prostate cancer-associated protein 6/ P501S/ prostein

SLC45A3 shows a predominantly homogenous Golgi staining pattern in prostatic epithelia. It is highly specific for prostate glandular cells and thus used in the differentiation of metastatic prostate cancers from other tumor types. SLC45A3 may be expressed in PSA-negative prostate tumors, and the use of these markers in conjunction offers increased sensitivity in the identification of prostate cancer metastases. Weaker expression of SLC45A3 has been noted in some aggressive tumors, correlating with increased Gleason scores and risk of cancer relapse.

IHC (Formalin/PFA-fixed paraffin-embedded sections) analysis of human prostate carcinoma tissue sections labeling SLC45A3 with purified ab137065 at 1/1000 dilution (0.128 µg/mL).

IHC (Formalin/PFA-fixed paraffin-embedded sections) analysis of human prostate carcinoma tissue sections labeling SLC45A3 with purified ab137065 at 1/1000 dilution (0.128 µg/mL).

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References

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Prostate-specific membrane antigen

Alternative names PSMA

PSMA is a type II membrane glycoprotein with both folate hydrolase and N-acetylated-alpha-linked-acidic peptidase (NAALAD) activity. In contrast to PSA, PSMA is expressed in high-grade prostatic adenocarcinomas and is associated with a high Gleason score. Detection of PSMA can help to identify metastatic prostate cancer in surgical specimens, yielding higher sensitivity than PSA alone. The high sensitivity and specificity of this marker for prostatic carcinoma make it useful to differentiate prostate from urothelial tumors.

Formalin-fixed, paraffin-embedded human prostate carcinoma tissue stained for PSMA using ab133579 at 1:300 in immunohistochemical analysis.

Formalin-fixed, paraffin-embedded human prostate carcinoma tissue stained for PSMA using ab133579 at 1:300 in immunohistochemical analysis.

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References

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Prostatic acid phosphatase

Alternative names PAP

PAP is an acid phosphatase enzyme expressed in prostate tissue at levels approximately two-fold greater than in other tissues. This biomarker has been investigated as a marker for metastatic prostate cancer due to its high and relatively specific expression in prostate epithelial cells and has been considered a target antigen in autologous cellular immunotherapy for patients with prostate cancer.

Knockdown of PAP expression is associated with the promotion of cell growth and tumorigenicity, leading to the development of castration-resistant androgen-specific prostate cancer.

Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) analysis of human prostate tissue sections labeling PAP with purified ab109004 at 1/40,000 dilution (0.0024 µg/mL).

Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) analysis of human prostate tissue sections labeling PAP with purified ab109004 at 1/40,000 dilution (0.0024 µg/mL).

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References

View 2 references for Prostatic acid phosphatase

NKX3.1

NKX3.1 is a prostate-specific androgen-regulated transcription factor important in normal prostate development, regulating the proliferation of glandular epithelium and in the formation of ducts in the prostate. Due to its highly specific expression in prostate epithelial cells, NKX3.1 can be used as a diagnostic biomarker for prostate cancer and other metastatic lesions originating in the prostate. Some studies show that NKX3.1 offers improved sensitivity over PSA for the identification of poorly differentiated metastatic prostate cancer.

Formalin-fixed paraffin-embedded human prostate hyperplasia tissue stained for NKX3.1 (ab196020) at 1/500 dilution. Negative control: Used PBS instead of primary antibody.

Formalin-fixed paraffin-embedded human prostate hyperplasia tissue stained for NKX3.1 (ab196020) at 1/500 dilution. Negative control: Used PBS instead of primary antibody.

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References

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p63

A member of the p53 protein family, p63 has pleiotropic functions, including cell proliferation, survival, apoptosis, differentiation, senescence, and aging. This biomarker shows a nuclear localization in basal cells of the prostate and is absent from usual-type acinar prostate cancers. Aberrant p63 expression in prostate cancers may represent a molecularly distinct subclass and rare tumor type, with some studies suggesting that further research of this biomarker may yield identification of the prostate cancer cell-of-origin.

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References

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ERG

ERG is a transcriptional regulator that is identified in approximately half of all prostatic adenocarcinomas. This emerging biomarker for prostate cancer localizes to the nucleus of cells and is commonly found as a fusion product with TMPRSS2 or SLC45A31. These ERG fusion products play an important role in the carcinogenesis of prostate cancer and may be predictive biomarkers of prostate cancer2,3.

Formalin-fixed paraffin-embedded human prostatic adenocarcinoma stage 3 tissue stained for ERG (ab92513) using unpurified antibody in immunohistochemical analysis.

Formalin-fixed paraffin-embedded human prostatic adenocarcinoma stage 3 tissue stained for ERG (ab92513) using unpurified antibody in immunohistochemical analysis.

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References

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PTEN

PTEN protein loss is an emerging IHC biomarker for prostate cancer. This protein is a cytosolic lipid phosphatase that negatively regulates AKT activity in cell growth to act as a tumor suppressor. Loss of PTEN expression is observed in approximately 20-30% of cases and considered prognostic for poor patient outcomes in this disease.

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References

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Fatty acid synthase

This enzyme plays a role in the synthesis of long-chain fatty acids. Fatty acid synthase overexpression is an emerging biomarker linked to prostate cancer carcinogenesis. Studies suggest that this emerging biomarker may act in cancer by inhibiting apoptosis and associate fatty acid synthase overexpression in prostate cancer IHC with increased Gleason score and more aggressive tumors.

Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) analysis of human breast cancer tissue sections labeling fatty acid synthase with purified ab128870 at 1:450 dilution (1.09 µg/mL).

Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) analysis of human breast cancer tissue sections labeling fatty acid synthase with purified ab128870 at 1:450 dilution (1.09 µg/mL).

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References

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FOXA1

Mutations in the FOXA1 transcription factor have been associated with tumor progression in prostate cancer. IHC analysis of FOXA1 as a prostate cancer biomarker has identified overexpression in prostate cancer metastases and linked this biomarker with more aggressive, castration-resistant cancer types. It may also act as an independent predictor of recurrence.

Formalin-fixed paraffin-embedded human prostate tissue labeled with FOXA1 (ab170933) with unpurified antibody at 1:100 in immunohistochemical analysis.

Formalin-fixed paraffin-embedded human prostate tissue labeled with FOXA1 (ab170933) with unpurified antibody at 1:100 in immunohistochemical analysis.

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References

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Prostate secretory protein 94

Alternative names PSP94

PSP94 (prostate secretory protein of 94 aa; also called PIP) is one of the major secretory proteins from the prostate gland. This potential prostate cancer biomarker shows decreasing expression as prostate cancer progresses from a hormone-dependent to a hormone-independent state with a complete lack of PSP94 production in highly advanced metastatic prostate cancer. This differential expression could make PSP94 a prognostic clinical marker for prostate cancer and could help distinguish patients with aggressive forms of prostate cancer.

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References

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Vascular endothelial growth factor

Alternative names VEGFA

VEGFA is a mediator of angiogenesis and tumor proliferation in many cancer types. Initial studies in prostate cancer suggest it may act as a prognostic biomarker for aggressive forms of prostate cancer and could be used to select prostate cancer patients suitable for novel anti-angiogenic therapies1. VEGFA expression has been shown to be significantly elevated in cases of prostatic cancer compared to benign hyperplasia, demonstrating it may serve as a potential diagnostic biomarker. Further, expression levels of VEGFA correlated with cancer grading, suggesting its utility as a prognostic marker2. View antibodies to VEGFA.

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References

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p27-kip1

In normal tissue, p27kip1 is a tumor suppressor that inhibits cyclin/cyclin-dependent kinase (CDK) cell cycle progression and regulates cancer cell invasion and migration. Decreased expression of p27kip1 is associated with poor patient prognosis in prostate adenocarcinomas. Additionally, cytoplasmic localization of p27kip1 has been linked to cyclin/CDK-independent roles in tumorigenicity.

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References

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Cytokeratin 5

Alternative names CK5

CK3, basic (type II) cytokeratin, acts as a dimer in partnership with cytokeratin 141. It is a member of the intermediate filament family of proteins, which provides the cell with a structural framework stretching from around the nucleus to desmosomes and hemidesmosomes. It is highly expressed in basal cells of prostate tissue, with diffuse cytoplasmic localization and perinuclear enhancement. This marker is used in conjunction with AMACR and PSA to rule out prostate cancer with increased accuracy2.

We recommend

Recommended Anti-wide spectrum Cytokeratin antibody ab9377

References

View 2 references for Cytokeratin 5

Cytokeratin 6

Alternative names CK6

CK6 is a basic cytokeratin that dimerizes with cytokeratin 16/17 for function1. CK6 is a cytoskeletal protein and serves as a marker for prostate basal cells, showing similar localization to CK5 of diffuse cytoplasmic staining with enrichment in the perinuclear area. Negative staining of this marker is often used in conjunction with CK5- and AMACR+ staining to diagnose problematic prostatic cancers2.

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References

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Kallikrein 2

Alternative names KLK2

Kallikrein 2 is highly expressed in the prostate gland under androgen control for expression1. It is a trypsin-like serine protease requiring post-translational modification for activity. In prostate tissue, KLK2 functions upstream of PSA to activate this prostate cancer biomarker; consequently, it is associated with seminal plasma liquefaction2.

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References

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References

Prostate specific antigen

Saini, S. PSA and beyond: alternative prostate cancer biomarkers. Cell Oncol (Dordr).  39 (2),97-106 (2016)

Alpha-methylacyl-CoA racemase

El Kassem, FA.,, Abulkheir, I., Sidom, N., et al. Role of immunohistochemical expression of AMACR as a prognostic and predictive biologic marker in advanced prostatic carcinoma. [http://dx.doi.org/10.1016/j.ejso.2016.06.190]. , (2016)

SLC45A3

Sheridan, T., Herawi, M. et al. The role of P501S and PSA in the diagnosis of metastatic adenocarcinoma of the prostate. Am. J. Surg. Pathol.  31  (9),1351-1355 (2007)

Prostate-specific membrane antigen

Bernacki, K.D., Fields, K.L. and , Roh, M.H. The utility of PSMA and PSA immunohistochemistry in the cytologic diagnosis of metastatic prostate carcinoma. Diagn Cytopathol.  42  (7),570-575 (2014)

Prostatic acid phosphatase

Muniyan S., Chaturvedi NK., Dwyer JG et al. Human Prostatic Acid Phosphatase: Structure, Function and Regulation. Int J Mol Sci.  14  (5),10438-10464 (2013)

Graddis TJ., McMahan CJ., Tamman J et al. Prostatic acid phosphatase expression in human tissues. Int J Clin Exp Pathol.  4  (3),295-306 (2011)

NKX3.1

Gurel B., Ali TZ., Montgomery EA, et al. NKX3.1 as a marker of prostatic origin in metastatic tumors. Am J Surg Pathol.  34  (8),1097-1105 (2010)

p63

Tan HL, Haffner MC, Esopi DM et al. Prostate adenocarcinomas aberrantly expressing p63 are molecularly distinct from usual-type prostatic adenocarcinomas. Mod Pathol.  28  (3),446-456 (2015)

ERG

Song C and , Chen H. Predictive significance of TMRPSS2-ERG fusion in prostate cancer: a meta-analysis. Cancer Cell International  18  ,177 (2018)

Chaux A , Albadine R, Toubaji A , et al. Immunohistochemistry for ERG expression as a surrogate for TMPRSS2-ERG fusion detection in prostatic adenocarcinomas Am J Surg Pathol.  35  (7),1014-1020 (2014)

Andrews C and , Humphrey PA. Utility of ERG versus AMACR expression in diagnosis of minimal adenocarcinoma of the prostate in needle biopsy tissue. Am J Surg Pathol.  38  (7),1007-1012 (2014)

PTEN

Geybels MS., Fang M,., Wright JL, et al. PTEN loss is associated with prostate cancer recurrence and alterations in tumor DNA methylation profiles. Oncotarget.  8  (48),84338-84348 (2017)

Fatty acid synthase

Migita T., Ruiz S., Fornari A, et al. Fatty Acid Synthase: A Metabolic Enzyme and Candidate Oncogene in Prostate Cancer. J Natl Cancer Inst.  101  (7),519-532 (2009)

Madigan AA., Rycyna KJ.., Parwani AV, et al. Novel nuclear localization of fatty acid synthase correlates with prostate cancer aggressiveness. Am J Pathol.  148  (8),2156-2162 (2014)

FOXA1

Gerhardt J., Montani M., Wild P, et al. FOXA1 promotes tumor progression in prostate cancer and represents a novel hallmark of castration-resistant prostate cancer. Am J Pathol.  180  (2),848-861 (2012)

Prostate secretory protein 94

Luebke AM., Attarchi-Tehrani A., Meiners J et al. Loss of PSP94 expression is associated with early PSA recurrence and deteriorates outcome of PTEN deleted prostate cancers. Cancer Biol Med.  16  (2),319-330 (2019)

Vascular endothelial growth factor

Kamath A., Helie M., Bifulco CB, et al. Lack of immunohistochemical detection of VEGF in prostate carcinoma. Appl Immunohistochem Mol Morphol.  17  (33),227-232 (2009)

Gautama KA et al. Angiogenesis in prostate cancer and benign prostatic hyperplasia assessed by VEGF and CD-34 IHC: A comparative clinico-pathological study. Science Direct  24  (2),98-103 (2018)

p27-kip1

Lee J & , Kim SS. The function of p27KIP1 during tumor development. Experimental & Molecular Medicine  41  ,767-771 (2009)

Cytokeratin 5

Pekny M, and , Lane EB. Intermediate filaments and stress. Exp Cell Res  10;313  (10),2244-2254 (2007)

Dabir PD., Ottosen P., et al. Comparative analysis of three- and two-antibody cocktails to AMACR and basal cell markers for the immunohistochemical diagnosis of prostate carcinoma. Diagn Pathol.  7  (81),16 (2012)

Cytokeratin 6

Coulombe PA., Tong X., Mazzalupo S, et al. Great promises yet to be fulfilled: defining keratin intermediate filament function in vivo. Eur J Cell Biol.  83  (11-12),735-746 (2004)

Trpkov K., Bartczak-McKay J and , Yilmaz A. Usefulness of cytokeratin 5/6 and AMACR applied as double sequential immunostains for diagnostic assessment of problematic prostate specimens. Am J Clin Pathol.  132  (2),211-220 (2009)

Kallikrein 2

Chao J., Chen L. , and Chai KX. Human Kallikrein-related Peptidase 2. In: Handbook of Proteolytic Enzymes.  Vol. 3  ,2762-2765 (2013)

Williams SA, et al. Prostate-Specific Antigen (PSA) Is Activated by KLK2 in Prostate Cancer Ex Vivo Models and in Prostate-Targeted PSA/KLK2 Double Transgenic Mice. Prostate.  15  (70(7)),788-796 (2010)