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Page 1: Prostate cancer diagnostic solutions Deliver diagnostic · PDF file4 Prostate cancer diagnostic solutions Prostate Carcinoma stained with VENTANA p504s (SP116) Rabbit Monoclonal Antibody

Prostate cancer diagnostic solutionsDeliver diagnostic confidence

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Page 2: Prostate cancer diagnostic solutions Deliver diagnostic · PDF file4 Prostate cancer diagnostic solutions Prostate Carcinoma stained with VENTANA p504s (SP116) Rabbit Monoclonal Antibody

2 Prostate cancer diagnostic solutions

Prostate cancer is a major public health concern

Prostate cancer is the fourth most common cancer in both sexes combined and the second common cancer in men.1 An estimated 1.1 million men are diagnosed with prostate cancer worldwide (see figure 1) with a main incidence in the America’s and Europe classified by the World Health Organization (WHO). Approximately 1 man in 7 will be diagnosed with prostate cancer during his lifetime.2 This makes prostate cancer the second most common cancer and the sixth most common cause of death from cancer, in men worldwide.3 Approximately 70% of prostate cancer cases are low risk, yet up to 90% are treated aggressively.4

Recent translational research is showing that much like soft tissue cancers, prostate cancer can now be molecularly subtyped with immunohistochemistry techniques, which may enable the identification of aggressive versus indolent disease.

We are committed to the development of innovative tools to better identify and subtype prostate cancer—so you can deliver the right test, with clinical confidence, in the shortest possible time.

“Patients come to prostatectomy with low volume, low grade neoplasms which do not benefit from surgery. On the other hand, there are patients with advanced disease with extra prostatic spread that, likewise, are not benefitted by surgery. Clearly, we need a presurgical assay which would identify these subtypes.”

— Dr. Raymond Nagle, University of Arizona

America

413,000Europe region

420,000

African region

52,000

Western Pacific region

153,000

Southeast Asian region

39,000

Figure 1: Global incidence prostate cancer1

180,890 new cases a year (US)2

26,120 deaths per year (US)2

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Prostate cancer diagnostic solutions 3

Why choose our solutions for prostate cancer diagnostics?

Our prostate cancer diagnostics deliver on key benefits valued by pathology professionals.

Analytical excellence Over the past few years, we have developed a leading, compre-hensive and differentiated prostate cancer immunohistochemical biomarker portfolio that is supported in current medical textbooks.5 The portfolio contains “gold standard,” peer-reviewed clones like p63 (4A4) and ERG (EPR3864), and emerging biomarkers like AR and EZH2.

Testing efficiency Delivering a comprehensive integrated solution, we empower you to run fully automated diagnostic assays on the market-leading VENTANA BenchMark IHC/ISH staining platforms that can free resources, reduce labor cost and speed time to results. Further confidence comes from our pre-diluted, optimized and ready-to-use reagents that consistently demonstrate high performance when compared to concentrated antibodies that require manual dilution and in-house validation.

Figure 2: Typical testing algorithm

Benign glands

DRE, PSA

Re-biopsy sooner

Re-biopsy sooner

Primary cancer screening

Prostate cancerNo biopsy

Continue screening

ASAP Benign glands

Active surveillance

Therapy (Radiation,

Hormone etc)Prostatectomy

Biopsy (H&E)

PIN4 (p63, HMWCK, p504s), ERG

Stage, Gleason grade

Unable to determine

High-grade PIN

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Page 4: Prostate cancer diagnostic solutions Deliver diagnostic · PDF file4 Prostate cancer diagnostic solutions Prostate Carcinoma stained with VENTANA p504s (SP116) Rabbit Monoclonal Antibody

4 Prostate cancer diagnostic solutions

Prostate Carcinoma stained with VENTANA p504s (SP116) Rabbit Monoclonal Antibody

Prostate carcinoma stained with VENTANA Basal Cell Cocktail (34βE12+p63)

Utilizing the Basal Cell Cocktail with anti-p504s provides greater sensitivity for the basal cell layer.25 This dual stain overcomes the problems of studying small lesions in needle biopsies and can be used as a routine test for prostate adenocarcinoma.8

VENTANA Basal Cell Cocktail (34βE12+p63) VENTANA Basal Cell Cocktail (34βE12+p63) is an antibody cocktail of p63 (4A4) and keratin (34βE12). p63 (4A4) reacts with the p63 molecule in the nuclei of human prostatic basal cells and urothelial tissues. Keratin (34βE12) reacts with Cytokeratins 1, 5, 10 and 14 and stains the cytoplasm of human prostatic basal cells. This antibody cocktail may be used to aid in the differentiation of benign lesions with basal cells from malignant prostate lesions lacking basal cells.

p504s (SP116) Rabbit Monoclonal Primary Antibodyp504s (SP116) Rabbit Monoclonal Primary Antibody (p504s (SP116) antibody) is directed against the p504s enzyme (also known as alpha-Methylacyl Coenzyme A racemase or AMACR). p504s is found to be overexpressed in human prostatic carcinoma, and exhibits a granular, cytoplasmic staining pattern in malignant glands and cells.8

Publications demonstrate the utility of p504s as an aid to the pathologist in recognizing small foci prostatic carcinoma when used to complement an absence of basal cell staining.9 This can be achieved in a dual stain with the Basal Cell Cocktail (34βE12 + p63) to optimize the use of limited available tissue on small focal cancer biopsies.25

Figure 3: Prostate carcinoma dual stained with p504s (SP116) Rabbit Monoclonal Primary Antibody in red, and VENTANA Basal Cell Cocktail (34βE12) in brown

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Page 5: Prostate cancer diagnostic solutions Deliver diagnostic · PDF file4 Prostate cancer diagnostic solutions Prostate Carcinoma stained with VENTANA p504s (SP116) Rabbit Monoclonal Antibody

Prostate cancer diagnostic solutions 5

Prostate carcinoma stained with VENTANA p63 (4A4) Mouse Monoclonal Primary Antibody

VENTANA p63 (4A4) Mouse Monoclonal Primary Antibody The VENTANA p63 (4A4) Mouse Monoclonal Primary Antibody is directed against the p63 molecule, which is highly expressed in the nuclei of human prostatic basal cells and urothelial tissues. This powerful tool can aid the pathologist in the differential diagnosis of prostate cancer in conjunction with morphological findings. Delivering consistently strong nuclear staining, the VENTANA p63 antibody may be used to aid in the differentiation of benign and malignant prostatic lesions.6,7,10

Prostate carcinoma stained with the NKX3.1 (EP356) Rabbit Monoclonal Primary Antibody

NKX3.1 (EP356) Rabbit Monoclonal Primary AntibodyNKX3.1 (EP356) Rabbit Monoclonal Primary Antibody is a sensitive and specific antibody for the detection of NKX3.1 protein. Publications demonstrate that the reliable detection of NKX3.1 may have utility in a number of clinical applications in prostatic carcinoma and breast carcinomas.33

• Prostatic carcinoma: There is a high frequency of NKX3.1 expression in prostatic adenocarcinoma with greater than 98% sensitivity and specificity.34, 35

• Gurel et al., demonstrated that nearly all cases of metastatic prostate adenocarcinoma were stained by NKX3.1.35 Gurel and Chuang showed that nearly all cases of urothelial carcinoma were negative for NKX3.1.35, 36

• NKX3.1-positive prostate carcinoma cells exhibit nuclear staining.35

100%98.5%

2.3%

80%

60%

40%

20%

0%

NKX

3.1

stai

ning

spe

cific

ity (%

)

Prostate adenocarcinoma Urothelial adenocarcinoma

Graph represents data from the package insert based on the following tissues: prostate adenocarcinoma, transitional cell carcinoma, clear cell renal cell carcinoma, metastatic renal cell carcinoma, metastatic transitional cell carcinoma, renal oncocytoma, papillary renal cell carcinoma and urothelial carcinoma.34

Figure 4: NKX3.1 demonstrates a high specificity for prostate adenocarcinomas and can be used to help distinguish between prostate and urothelial carcinomas.35, 36

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6 Prostate cancer diagnostic solutions

Emerging markers—investing in future clinical utility

Prostate carcinoma stained with ERG (EPR3864) Rabbit Monoclonal Primary Antibody

ERG (EPR3864) Rabbit Monoclonal Primary Antibody Research has demonstrated that the TMPRESS2:ERG rearrangement occurs in approximately 50% of prostate cancer patients, does not occur in normal tissue, and describes a molecular subtype that is associated with androgen-driven prostate cancer. As this subtype is the most prevalent in prostate cancer, there has been tremendous diagnostic, prognostic and predictive interest in the ERG biomarker. 26, 28, 31

The ERG (EPR3864) Rabbit Monoclonal Primary Antibody is capable of detecting:

• Truncated ERG resulting from TMPRSS2:ERG (or other ERG gene fusions)

• Wild type ERG (most notably expressed in vessel endothelium)

Double immunohistochemical staining of highly specific ERG (EPR3864) with highly sensitive p63 (4A4) may be potentially useful in the work-up of difficult prostate biopsies.29

15–20% of HGPIN lesions harbor ERG rearrangement. Studies suggest that TMPRSS2:ERG fusion positive HGPIN may be an indication of more aggressive disease.26, 27, 30

ERG staining shows utility in diagnostically challenging biopsies and may be useful in molecularly subtyping prostate cancer and in stratifying isolated high-grade prostatic intraepithelial neoplasia by risk of subsequent cancer. 32

VENTANA PTEN (SP218) Rabbit Monoclonal Primary AntibodyThe VENTANA PTEN (SP218) Rabbit Monoclonal Primary Antibody is directed against the protein tyrosine phosphatase encoded by the tumor suppressor gene phosphatase and tensin homolog (PTEN) at chromosome 10q23.3, which is also known as the gene mutated in multiple advanced cancers (MMAC1).12, 13

The PTEN protein is identical to transforming growth factor-B-regulated and epithelial cell-enriched phosphatase (TEP1), and plays an important role in controlling cell survival and cell cycle progression as a negative regulator of the phosphoinositide 3-kinase/Akt pathway.14-16

Reduced or absent PTEN protein expression has been identified by immunohistochemical analyses in several cancers, including prostate, breast, thyroid, endometrial, gastric, non-small cell lung, pancreatic and colorectal.17-24 The PTEN protein is localized in the cytoplasm and nucleus and is constitutively expressed in non-neoplastic tissues.

Prostate cancer stained with the VENTANA PTEN (SP218) Rabbit Monoclonal Primary Antibody

Note: Sale of this product does not convey any license rights to use this product to detect

PTEN or PTEN expression in prostate cancer to assess disease-specific mortality, disease

recurrence, or disease progression. Customers that wish to use this product for such

purposes should contact Myriad Genetics, Inc. for a license, or otherwise ascertain whether

such use requires a license from Myriad (US only).

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Prostate cancer diagnostic solutions 7

1. http://globocan.iarc.fr/old/FactSheets/cancers/prostate-new.asp#MORTALITY

2. American Cancer Society. What are the key statistics about prostate cancer? American Cancer

Society Website. http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-can-

cer-key-statistics. Revised 14 Dec 2012. Accessed 9 Nov 2012.

3. Cancer Research UK. Prostate Cancer. http://www.cancerresearchuk.org/cancer-info/

cancerstats/world/prostate-cancer-world/

4. Hayes et al. Active Surveillance Compared With Initial Treatment for Men With Low-Risk

Prostate Cancer A Decision Analysis. JAMA. 2010; 304(21): 2373-2380. doi:10.1001/

jama.2010.1720.

5. R B Shah, M Zhou, Prostate Biopsy Interpretation: an Illustrated Guide. New York University,

NewYork, USA; 2012.

6. Weinstein MH, et al. Diagnostic utility of immunohistochemical staining for p63, a sensitive

marker of prostatic basal cells. Mod Pathol 2002; 15:1302-1308.

7. Harton AM, et al. p63 immunocytochemistry improves accuracy of diagnosis with fine-needle

aspiration of the breast. AM J Clin Pathol 2007;128:80-85.

8. Jiang Z, et al. Using an AMACR (P504S)/34βe12/p63 cocktail for the detection of small focal

prostate carcinoma in needle biopsy specimens. AM J Clin Pathol 2005; 123(2): 231 -236.

9. Epstein J I; Diagnosis of limited adenocarcinoma of the prostate. Histopathology 2012; 28-40.

10. Parsons et al. p63 protein expression is rare in prostate adenocarcinoma: implications for

cancer diagnosis and carcinogenesis. Urology. 2001; 58:619-24.

11. Zhou M et al. Basal cell cocktail (34βe12 + p63) improves the detection of prostate basal cells.

AM J Surg Pathol 2003; 27: 365-71.

12. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie r,

Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parson R. PTEN, a

putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate

cancer. Science. 1997;275:1943-1947.

13. Steck PA, Pershouse MA, Jasser SA, Yung WKA, Lin H, Ligon AH, Langford LA, Baumgard ML,

Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DHF, Tavtigian SV. Identification of a

candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in

multiple advanced cancers. Nat Genet 1997;15:356-362.

14. Li D-M, Sun H. TEP1, encoded by a candidate tumor suppressor locus, is a novel protein

tyrosine phosphatase regulated by transforming growth factor B1. Cancer Res. 1997;57:2124-

2129.

15. Wu X, Senechal K, Neshat MS, Whang YE, Sawyers CL. The PTEN/MMAC1 tumor suppressor

phosphatase functions as a negative regulator of the phosphoinositide 3-kinase/Akt pathway.

Proc Natl Acad Sci. 1998;95:15587-15591.

16. Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirstos C, Sasaki T, Ruland J, Penninger

JM, Siderovski DP, Mak TW. Negative regulation of PKB/Akt-dependent cell survival by the

tumor suppressor PTEN. Cell. 1998;95:29-39.

17. Whang YE, Wu X, Suzuki H, Reiter RE, Tran C, Vassella RL, Said JW, Isaacs WB, Sawyers CL.

Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer

through loss of expression. Proc Natl Acad Sci. 1998;95:5246-5250.

18. Perren A, Weng L-P, Boag AH, Ziebold U, Thakore K, Dahia PLM, Komminoth P, Lees JA,

Mulligan LM, Mutter GL, Eng C. Immunohistochemical evidence of loss of PTEN expression in

primary ductal adenocarcinomas of the breast. Am J Pathol. 1999;155:1253-1260.

19. Gimm O, Perren A, Weng L-P, Marsh DJ, Yeh JJ, Ziebold U, Gil E, Hinze R, Delbridge L, Lees JA,

Mutter GL, Robinson BG, Komminoth P, Dralle H, Eng C. Differential nuclear and cytoplasmic

expression of PTEN in normal thyroid tissue, and benign and malignant epithelial thyroid

tumors. Am J Pathol. 2000;156:1693-1700.

20. Mutter GL, Lin M-C, Fitzgerald JT, Kum JB, Baak JPA, Lees JA, Weng L-P, Eng C. Altered PTEN

expression as a diagnostic marker for the earlest endometrial precancers. J Natl Cancer Inst.

2000;92:924-931.

21. Fei G, Ebert MPA, Mawrin C, Leodolter A, Schmidt N, Dietzmann K, Malfertheiner P. Reduced

PTEN expression in gastric cancer and in the gastric mucosa of gastric cancer relatives. Eur J

Gastoenterol Hepatol 2002;14:297-303.

22. Soria J-C, Lee H-Y, Lee JI, Wang L, Issa J-P, Kemp BL, Liu DD, Kurie JM, Mao L, Khuri FR. Lack

of PTEN expression in non-small cell lung cancer could be related to promoter methylation.

Clin Cancer Res. 2002;8:1178-1184.

23. Asano T, Yao Y, Zhu J, Li D, Abbruzzese JL, Reddy SAG. The Pi 3-kinase/Akt signaling pathway

is activated due to aberrant PTEN expression and targets transcription factors NF-κB and

c-Myc in pancreatic cancer cells. Oncogene. 2004;23:8571-8580.

References

Product Catalog number Ordering code Tests

Androgen Receptor (AR) (SP107) Rabbit Monoclonal Primary Antibody 760-4605 06523838001 50

Basal Cell Cocktail (34βE12+p63), VENTANA 790-4536 06364497001 50

Basal Cell Cocktail (34βE12+p63), VENTANA 790-1010 06419445001 250

Cytokeratin 5/6 (D5/16B4) Mouse Monoclonal Primary Antibody 790-4554 06478441001 50

ERG (EPR3864) Rabbit Monoclonal Primary Antibody 790-4576 06478450001 50

EZH2 (SP129) Rabbit Monoclonal Primary Antibody 790-4651 06522858001 50

NKX3.1 (EP356) Rabbit Monoclonal Primary Antibody 760-5086 07859759001 50

p504s (SP116) Rabbit Monoclonal Primary Antibody 790-6011 08035130001 50

p63 (4A4), VENTANA Mouse Monoclonal Primary Antibody 790-4509 05867061001 50

Prostate Specific Antigen (PSA) Rabbit Polyclonal Primary Antibody 760-2506 05266939001 50

Prostate-Specific Antigen (PSA) (ER-PR8) Mouse Monoclonal Primary Antibody 760-4271 05269334001 50

Prostate-Specific Antigen (PSA) (ER-PR8) Mouse Monoclonal Primary Antibody (RUO) 760-4930 07239327001 50

Prostatic Acid Phosphatase (PSAP) (PASE/4LJ) Mouse Monoclonal Primary Antibody 760-4272 05269342001 50

PTEN (SP218), VENTANA Rabbit Monoclonal Primary Antibody 790-5097 07970200001 50

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Roche Diagnostics (Schweiz) AGIndustriestrasse 76343 RotkreuzTel. 041 799 61 00www.roche-diagnostics.ch

www.roche.com www.ventana.com

© 2017 Ventana Medical Systems, Inc.

VENTANA and BENCHMARK are trademarks of Roche. All other trademarks are the property of their respective owners. 7009B-6 0317 RTDPC-ASFASA-0111

Join us in our quest to improve the lives of prostate cancer patients worldwide. Experience the confidence that comes from bringing the gold standard in prostate diagnostics to your practice—and patients—today. Contact your local Account Manager or visit us on the web at: www.ventana.com/prostate.

24. Frattini M, Saletti P, Romagnani E, Martin V, Molinari F, Ghisletta M, Camponovo A, Etienne LL,

Cavalli F, Mazzucchelli L. PTEN loss of expression predicts cetuximab efficacy in metastatic

colorectal cancer patients. Br J Cancer. 2007;97:1139-1145.

25. Ng, et al. Is Triple Immunostaining with 34βE12, p63, and Racemase in Prostate Cancer

Advantageous? : A Tissue Microarray Study. American Journal of Clinical Pathology, 2007; 127:

248-253.

26. Shah R B, et al. The diagnostic use of ERG in resolving an “atypical glands suspicious for cancer”

diagnosis in prostate biopsies beyond that provided by basal cell and α-methylacyl-CoAracemase

markers. Human pathology. 2013; 44(5): 786 -794.

27. Park et al. TMPRSS2:ERG Gene Fusion Predicts Subsequent Detection of Prostate Cancer in

Patients With High-Grade Prostatic Intraepithelial Neoplasia. Journal of Clinical Oncology. 2013:

Published online before print December 2, 2013. doi: 10.1200/JCO.2013.49.8386.

28. Weischenfeldt et al. Integrative Genomic Analyses Reveal an Androgen-Driven Somatic

Alteration Landscape in Early-Onset Prostate Cancer. Cancer Cell. 2013; 23:159-170.

29. Yaskiv, Oksana et al. The Utility of ERG/P63 Double Immunohistochemical Staining in the

Diagnosis of Limited Cancer in Prostate Needle Biopsies. The American Journal of Surgical

Pathology. 2011; 35(7): 1062 -1068.

30. Mosquera, J.-M. et al. Characterization of TMPRSS2-ERG Fusion High-Grade Prostatic

Intraepithelial Neoplasia and Potential Clinical Implications. Clinical Cancer Research. 2008;

14(11): 3380 -3385.

31. Park, K et al. Antibody-based detection of ERG rearrangement-positive prostate cancer.

Neoplasia. 2010; 12(7): 590.

32. Tomlins, et al. Antibody-Based Detection of ERG Rearrangements in Prostate Core Biopsies,

Including Diagnostically Challenging Cases: ERG Staining in Prostate Core Biopsies. Arch Pathol

Lab Med. 2012. 136(8): 935-946.

33 Asch-Kendrick R, et al. NKX3.1 is expressed in ER-positive and AR-positive primary breast

carcinomas. J Clin Pathol. 2014; 67:768-71.

34. NKX3.1 (EP356) Package Insert

35. Gurel B, et al. NKX3.1 as a marker of prostatic origin in metastatic tumors. Am J Surg Pathol. 2010;

34:1097-1105.

36. Chuang A, et al. Immunohistochemical differentiation of high-grade prostate carcinoma from

urothelial carcinoma. Am J Surg Pathol. 2007; 31:1246-55.

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