Expression of ETS related gene (ERG) and phosphatase and tensin homolog (PTEN) correlates with prostate cancer capsular penetration

Patent metadata

Field	Value
Publication number	US-9435812-B2
Application number	US-201213596266-A
Country	US
Kind code	B2
Filing date	Aug 28, 2012
Priority date	Aug 31, 2011
Publication date	Sep 6, 2016
Grant date	Sep 6, 2016

Abstract

The disclosure provides methods for characterizing a prostate cancer sample by detecting expression of ERG, PTEN or both, changes in which relative to a normal control are shown herein to be correlated with prostate cancer capsular penetration and more aggressive forms of prostate cancer. Such methods are useful for the prognosis of prostate cancer capsular penetration and for making treatment decisions in patients with prostate cancer that has penetrated the capsule. Also provided are kits that can be used with such methods.

First claim

We claim:

1. A method for determining risk that a prostate cancer will penetrate the prostatic capsule, comprising:
contacting a prostate cancer sample isolated from a subject with an ETS related gene (ERG)-specific antibody and a phosphatase and tensin homolog (PTEN)-specific antibody;
measuring increased protein expression of ERG in the prostate cancer sample relative to a control representing ERG protein expression expected in a normal prostate sample;
measuring decreased PTEN in the prostate cancer sample relative to a control representing PTEN protein expression expected in a normal prostate sample;
determining that there is a higher risk that the prostate cancer has penetrated or will likely penetrate the prostatic capsule based on the ERG measuring and the PTEN measuring; and
administering a therapeutic agent for treating prostate cancer to the subject from which the prostate cancer sample was obtained, performing a prostatectomy on the subject from which the prostate cancer sample was obtained, or combinations thereof.

2. The method of claim 1 , wherein the prostate cancer sample is a prostate cancer sample that has not penetrated the prostatic capsule, and the method determines that the risk that the prostate cancer will penetrate the prostatic capsule in the future is at least four-times more likely when increased expression of ERG and decreased expression of PTEN is measured in the prostate cancer sample relative to the control.

3. The method of claim 1 , wherein it is not known whether the prostate cancer sample has penetrated the prostatic capsule prior to performing the method, and the method determines that the cancer has penetrated the prostatic capsule when increased expression of ERG and decreased expression of PTEN is measured in the prostate cancer sample relative to the control.

4. The method of claim 1 , further comprising:
measuring expression of one or more other prostate cancer-related molecules in the sample; and
comparing expression of the one or more other prostate cancer related molecules in the prostate cancer sample to a control representing expression of the one or more other prostate cancer-related molecules expected in a normal prostate sample.

5. The method of claim 1 , wherein the prostate cancer sample is a fixed, wax-embedded prostate cancer tissue sample.

6. The method of claim 1 , wherein the prostate cancer sample is collected after prostate cancer diagnosis and after prostatectomy in the subject.

7. The method of claim 1 , wherein the prostate cancer sample is collected from tissue removed during a prostatectomy.

8. The method of claim 1 , wherein the ERG-specific antibody is a rabbit monoclonal antibody produced from hybridoma clone EPR 3864 and the PTEN-specific antibody is a rabbit monoclonal antibody produced from hybridoma clone 138G6.

9. The method of claim 1 , further comprising generating a report, wherein the report comprises a risk that a prostate cancer will penetrate the prostatic capsule.

10. The method of claim 1 , wherein the therapeutic agent is radiation, a chemotherapeutic, or a hormone.

11. The method of claim 10 , wherein the chemotherapeutic comprises temozolomide or docetaxel.

Assignees

• Pestano Gary
• Nagle Ray B
• Cortez Connie
• Vanpatten Kristie A
• Algotar Amit M
• Ventana Med Syst Inc
• Univ Arizona

Inventors

• Pestano Gary
• Nagle Ray B
• Cortez Connie
• Vanpatten Kristie A
• Algotar Amit M

Classifications

• G01N33/57575

  involving oncogenic proteins · CPC title

• G01N33/57555

  of the prostate · CPC title

• C12Q2600/118

  Prognosis of disease development · CPC title

• C12Q2600/16

  Primer sets for multiplex assays · CPC title

• C12Q1/6886 Primary

  for cancer (immunoassay for cancer G01N33/575) · CPC title