Grading, staging and prognosing cancer using osteopontin-C

Patent metadata

Field	Value
Publication number	US-9873915-B2
Application number	US-68231008-A
Country	US
Kind code	B2
Filing date	Oct 16, 2008
Priority date	Oct 16, 2007
Publication date	Jan 23, 2018
Grant date	Jan 23, 2018

Abstract

The present disclosure provides methods and kits that can be used to determine the grade or stage of a breast or other cancer, such as a ductal carcinoma in situ (DCIS). By determining the grade, stage, or aggressiveness of a cancer, appropriate therapeutic regiments can be selected and administered to the patient with the cancer. The method includes detecting osteopontin-c (OPN-c), wherein the presence of high amounts of OPN-c in the cancer sample indicates that the subject has a more aggressive form of cancer (e.g., grade 3).

First claim

We claim:

1. A method of treating a patient having a triple negative breast cancer tumor, the method comprising:
(I) grading the triple negative breast cancer tumor in the patient by:
(1) obtaining a sample of the triple negative breast cancer tumor from the patient;
(2) contacting the sample of the triple negative breast cancer tumor with an antibody that specifically binds to the splice junction of the OPN-c protein under conditions suitable to form a complex of the OPN-c protein and the antibody, wherein the antibody is anti-human OPN-c IgY;
(3) detecting the expression intensity level of the OPN-c protein in the sample contacted with the antibody in (I)(2) via immunohistochemical staining; and
(4) quantifying the expression intensity level of the OPN-c protein detected in the sample in (I)(3); and
(5) grading the tumor on the basis of OPN-c expression intensity level; and

(II) treating the patient with:
(1) an aggressive therapeutic protocol when the triple negative breast cancer tumor has a grade of 2 or 3 on the basis of OPN-C protein expression level, wherein the aggressive therapeutic protocol comprises mastectomy or lumpectomy combined with radiotherapy and/or chemotherapy; and
(2) a less aggressive therapeutic protocol when the triple negative breast cancer tumor has a grade of 1 on the basis of OPN-C protein expression level, wherein the less aggressive therapeutic protocol consists of lumpectomy.

2. A method for treating a breast cancer patient suspected of having a triple negative breast cancer, the method comprising:
(I) assessing triple negative breast cancer in the patient by:
(1) obtaining a breast cancer tumor sample from the patient; and
(2) detecting an expression level of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in the tumor sample, wherein the expression level of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) is indicative of triple negative breast cancer;

(II) grading the tumor sample when triple negative breast cancer is indicated in (I)(2) by:
(1) contacting the tumor sample with an antibody that specifically binds to the splice junction of the OPN-c protein under conditions suitable to form a complex of the OPN-c protein and the antibody, wherein the antibody is anti-human OPN-c IgY;
(2) detecting the expression intensity level of the OPN-c protein in the tumor sample contacted with the antibody in (II)(1) via immunohistochemical staining; and
(3) quantifying the expression intensity level of the OPN-c protein detected in the tumor sample in (II)(2); and
(4) grading the triple negative breast cancer on the basis of OPN-c expression intensity level; and

(III) treating the patient with:
(1) an aggressive therapeutic protocol when the triple negative breast cancer tumor has a grade of 2 or 3 on the basis of OPN-C protein expression level, wherein the aggressive therapeutic protocol comprises mastectomy, or comprises lumpectomy combined with radiotherapy and/or chemotherapy; or
(2) a less aggressive therapeutic protocol when the triple negative breast cancer tumor has a grade of 1 on the basis of OPN-C protein expression level, wherein the less aggressive therapeutic protocol consists of lumpectomy.

3. The method of claim 1 or 2 , wherein the triple negative breast cancer is ductal carcinoma in situ (DCIS).

4. The method of claim 1 , wherein the triple negative breast cancer tumor has no detectable level of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).

5. The method of claim 1 , wherein the expression level of the OPN-c protein detected in the sample in (I)(3) is quantified with a staining intensity score.

6. The method of claim 1 , wherein:
the expression level of the OPN-c protein detected in the sample in (I)(3) is quantified with a staining intensity score;
a staining intensity score of 0-1.5 is indicative of a grade 0-1 tumor;
a staining intensity score of 2-2.5 is indicative of a grade 2 tumor; and
a staining intensity score of 3 or more is indicative of a grade 3 tumor.

7. The method of claim 2 , wherein the expression level of the OPN-c protein detected in the sample in (II)(2) is quantified with a staining intensity score.

8. The method of claim 2 , wherein:
the expression level of the OPN-c protein detected in the sample in (II)(2) is quantified with a staining intensity score;
a staining intensity score of 0-1.5 is indicative of a grade 0-1 tumor;
a staining intensity score of 2-2.5 is indicative of a grade 2 tumor; and
a staining intensity score of 3 or more is indicative of a grade 3 tumor.

9. The method of claim 1 , wherein the tumor grade is made on the basis of OPNc expression without consideration of OPNa or OPNb expression.

10. The method of claim 2 , wherein the tumor grade is made on the basis of OPNc expression without consideration of OPNa or OPNb expression.

Assignees

• Mirza Mana
• Shaughnessy Elizabeth
• Weber Georg F
• Hurley John K
• Vanpatten Kristie A
• Pestano Gary
• Ventana Med Syst Inc
• Univ Cincinnati

Inventors

• Mirza Mana
• Shaughnessy Elizabeth
• Weber Georg F
• Hurley John K
• Vanpatten Kristie A
• Pestano Gary

Classifications

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• C12Q2600/158

  Expression markers · CPC title

• C12Q1/6886 Primary

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

• C12Q2600/112

  Disease subtyping, staging or classification · CPC title

• A61K47/6855

  the tumour determinant being from breast cancer cell · CPC title