VENTANA PTEN (SP218)Rabbit Monoclonal Primary AntibodyExploring cancer pathways

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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).1,2

The PTEN protein is identical to transforming growth factor-beta-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.3-5

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.6-13 The PTEN protein is localized in the cytoplasm and nucleus and is constitutively expressed in non-neoplastic tissues. PTEN and the PI3K pathwayThe phosphatidylinositol 3-kinase (PI3K) pathway can be activated by growth factors binding to cell-surface receptors. PI3K converts PIP2* to PIP.3** Protein kinase B is activated following recruitment to the cell surface by PIP3 and acts downstream of PI3K to regulate many cellular processes such as cell survival and growth. PTEN is a negative regulator of the PI3K pathway and works by dephosphorylating (disabling) PIP3 which results in a decrease in Akt activity (Figure 1).

†Loss of expression of PTEN can be due to mutation, loss of heterozygosity or epigenetic factors, such as promoter hypermethylation or altered expression of microRNAs (miR?21 and others).14

PTEN is a commonly lost tumor suppressor in human cancer.

Monoallelic loss of PTEN

Glioblastoma Colon cancer Breast cancer Lung cancer Prostate cancer Gastric cancer

75% 20% 40-50%37 % 42% 47%

Biallelic mutation of PTEN

Endometrial cancer Glioblastoma Prostate cancer Breast cancer Colorectal cancer

50% 30% 10% 5% 7%

Loss of expression of PTEN†

Endometrial cancer Prostate cancer Breast cancer Ovarian cancer Glioblastoma Melanoma

NA NA NA NA NA NA

The VENTANA PTEN (SP218) Rabbit Monoclonal Primary Antibody is a ready-to-use IVD IHC antibody for evaluating expression of PTEN protein using the OptiView DAB IHC Detection Kit.

p110PIP3

PIP2

p85

P13K

mTOR FOXO

Akt

PTENTyrosinekinasedomain

ApoptosisCell growth

Figure 1PTEN as part of the PI3K pathway Aberrant activation of the phosphatidylinositol 3-kinase (PI3K) pathway results in the survival and proliferation of tumor cells in many human cancers.15-17

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Presence of VENTANA PTEN (SP218) staining in prostate cancer, 10x

Presence of VENTANA PTEN (SP218) staining in NSCLC, 10x Absence of VENTANA PTEN (SP218) staining in NSCLC, 10x

Absence of VENTANA PTEN (SP218) staining in prostate cancer, 10x

Presence of VENTANA PTEN (SP218) staining in ductal breast carcinoma, 10x Absence of VENTANA PTEN (SP218) staining in ductal breast carcinoma, 10x

The clinical interpretation of any staining, or the absence of staining, must be complemented by histological studies and evaluation of proper controls. Evaluation must be made by a qualified pathologist within the context of the patient’s clinical history and other diagnostic tests. This antibody is intended for in vitro diagnostic (IVD) use.

Intended Use StatementThe VENTANA PTEN (SP218) Rabbit Monoclonal Primary Antibody is intended for laboratory use in the qualitative detection of the PTEN protein in formalin-fixed, paraffin-embedded tissue. It is intended to be stained with the VENTANA BenchMark ULTRA immunohistochemical automated slide stainer.

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www.roche.com www.ventana.com

© 2016 Ventana Medical Systems, Inc.

VENTANA, BENCHMARK and OPTIVIEW are trademarks of Roche. All other trademarks are the property of their respective owners. 62131A-1 0616 RTDPC-CDx-0111

References

1. 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.

2. 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.

3. Li D-M, Sun H. TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta1. Cancer Res. 1997;57:2124-2129.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

Automation: Optimized for use on the VENTANA BenchMark ULTRA IHC/ISH instrument Detection: Optimized with OptiView DAB IHC Detection Kit (06396500001)

9. 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 earliest endometrial precancers. J Natl Cancer Inst. 2000;92:924-931.

10. 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.

11. 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.

12. 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.

13. 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.

14. Rodon J, Dienstmann R, Serra V, Tabernero J. Development of PI3K inhibitors: lessons learned from early clinical trials. Nat Rev Clin Oncol. 2013;10:143-153.

15. Myers AP, Cantley LC. Targeting a common collaborator in cancer development. Sci Transl Med. 2010;2:48ps45. PMID: 20826838

16. Song L, Xiong H, Li J, et al. Sphingosine kinase-1 enhances resistance to apoptosis through activation of PI3K/Akt/NF-ΚB pathway in human non-small cell lung cancer. Clin Cancer Res. 2011;17:1839-1849. PMID: 21325072

17. Rodon J, Dienstmann R, Serra V, Tabernero J. Development of PI3K inhibitors: lessons learned from early clinical trials. Nat Rev Clin Oncol. 2013;10:143-153. PMID: 23400000

VENTANA PTEN (SP218) Rabbit Monoclonal Primary AntibodyCatalog number 790-5097 07970200001Quantity 50 tests

Positive control Pancreas (islet cells)Species RabbitLocalization Cytoplasmic and/or nuclear

*PIP2 – Phosphatidylinositol 4,5-bisphosphate**PIP3 – Phosphatidylinositol (3,4,5)-trisphosphate

Roche Diagnostics (Schweiz) AG Industriestrasse 7 CH-6343 Rotkreuz Schweiz Tel: +41 (0)41 799 61 00 Fax: +41 (0)41 799 65 45

www.roche-diagnostics.ch www.ventana.com

© 2016 Ventana Medical Systems, Inc. All trademarks mentioned enjoy legal protection.

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