Methods for the diagnosis and prognosis of cancer

• US 5,840,506 A
• Filed: 04/04/1997
• Issued: 11/24/1998
• Est. Priority Date: 06/05/1996
• Status: Expired due to Term

• Current Assignee: Thomas Jefferson University (Main Line Health System)
• Original Assignee: Thomas Jefferson University (Main Line Health System)
• Inventors: Giordano, Antonio
• Primary Examiner(s): HUFF, SHEELA JITENDRA
• Application Number:
  US08/832,877
• Time in Patent Office: 599 Days
• Field of Search: 530/387.7, 436/518-523, 435/6, 435/7.1, 435/7.2, 435/7.21, 435/7.23, 435/7.9-7.95
• US Class Current: 435/7.23
• CPC Class Codes: G01N 33/57407 Specifically defined cancers
• CPC Class Codes: G01N 33/57496 involving intracellular compounds

Abstract

The invention provides diagnostic and prognostic methods which comprise determining the level of expression of the tumor suppressor gene pRb2/p130. Because the relative level of pRb2/p130 expression correlates with tumor grade and patient prognosis, these methods may be used to detect the presence of cancer, to make treatment decisions, and to predict the risk of cancer in disease-free individuals.

Claims

1. A method for determining a prognosis in a patient afflicted with cancer comprising determining the expression level of the pRb2/p130 gene in a sample from the patient, a decreased level of pRb2/p130 expression being indicative of an unfavorable prognosis.

2. The method of claim 1 wherein determining the expression level of the pRb2/p130 gene comprises determining the number of RNA transcripts of the gene relative to a standard number of said transcripts.

3. The method of claim 1 wherein determining the expression level of the pRb2/p130 gene comprises determining the level of the pRb2/p130 protein relative to a standard level of said protein.

4. The method of claim 3 wherein the level of the pRb2/p130 protein is determined by contacting the sample with an antibody which binds the pRb2/p130 protein.

5. The method of claim 1 wherein the sample is obtained from the patient prior to treatment of the patient with radiotherapy or chemotherapy.

6. The method of claim 1 wherein the cancer is a gynecologic cancer.

7. The method of claim 6 wherein the cancer is endometrial carcinoma.

8. The method of claim 7 wherein the sample comprises endometrial tissue.

9. The method of claim 8 wherein the endometrial tissue comprises a tumor.

10. The method of claim 6 wherein the cancer is ovarian cancer.

11. The method of claim 1 wherein the cancer is non-small cell lung cancer.

12. A method for identifying individuals at risk for cancer, or individuals at risk for the recurrence of cancer after treatment, comprising:

determining the level of expression of the pRb2/p130 gene in tissue sampled from an individual; and

comparing the pRb2/p130 expression level in the sampled tissue with a normal pRb2/p130 expression level.

13. The method of claim 12 wherein determining the expression level of the pRb2/p130 gene comprises determining the number of RNA transcripts of the gene relative to a standard number of said transcripts.

14. The method of claim 12 wherein determining the expression level of the pRb2/p130 gene comprises determining the level of the pRb2/p130 protein relative to a standard level of said protein.

15. The method of claim 14 wherein the level of the pRb2/p130 protein is determined by contacting the sample with an antibody which binds the pRb2/p130 protein.

16. The method of claim 12 wherein the cancer is a gynecologic cancer.

17. The method of claim 16 wherein the cancer is endometrial carcinoma.

18. The method of claim 16 wherein the cancer is ovarian cancer.

19. The method of claim 12 wherein the cancer is non-small cell lung cancer.

20. A method for grading a cancer comprising

determining the level of expression of the pRb2/p130 gene in a sample of tissue from a patient suffering from cancer, the level of expression being indicative of the grade of the cancer.

21. The method of claim 20 wherein determining the level of expression of the pRb2/p130 gene comprises determining the number of RNA transcripts of the gene in the sampled tissue relative to a standard number of said transcripts.

22. The method of claim 20 wherein determining the level of expression of the pRb2/p130 gene comprises determining the level of the corresponding pRb2/p130 protein in the sampled tissue relative to a standard level of said protein.

23. The method of claim 22 wherein the level of the protein in the sampled tissue is determined by an immunoassay whereby an antibody which binds said pRb2/p130 protein is contacted with said sampled tissue.

24. The method of claim 20 wherein the cancer is a gynecologic cancer.

25. The method of claim 24 wherein the cancer is endometrial carcinoma.

26. The method of claim 24 wherein the cancer is ovarian cancer.

27. The method of claim 20 wherein the cancer is non-small cell lung cancer.

28. The method of claim 27 wherein the cancer is a squamous cell carcinoma or an adenocarcinoma.

29. A method for detection of a cancerous disease state in a tissue of a patient comprising determining the level of the pRb2/p130 protein in a sample of the patient tissue relative to a standard level of said protein, a decreased level of said pRb2/p130 protein being indicative of the presence of cancer.

30. The method of claim 29 wherein the level of the pRb2/p130 protein is determined by contacting the sample with an antibody which binds the pRb2/p130 protein.

31. A method for detection of a gynecological cancer in a tissue of a patient comprising determining the expression level of the pRb2/p130 gene in a sample of the patient tissue, a decreased level of pRb2/p130 expression being indicative of the presence of gynecological cancer.

32. The method of claim 31 wherein the cancer is endometrial carcinoma.

33. The method of claim 31 wherein the cancer is ovarian cancer.

34. A method for detection of non-small cell lung cancer in a tissue of a patient comprising determining the expression level of the pRb2/p130 gene in a sample of the patient tissue, a decreased level of pRb2/p130 expression being indicative of the presence of non-small cell lung cancer.