التفاصيل البيبلوغرافية
| العنوان: |
AROMATASE EXPRESSION PREDICTS SURVIVAL IN WOMEN WITH NON-SMALL CELL LUNG CANCER |
| Document Number: |
20100331203 |
| تاريخ النشر: |
December 30, 2010 |
| Appl. No: |
12/681579 |
| Application Filed: |
October 06, 2008 |
| مستخلص: |
The present invention relates to the discovery that the level of aromatase polypeptide expression in non-small cell lung carcinomas can be used for example to provide information useful in prognostic and therapeutic methodologies in women having or suspected of having this cancer. |
| Inventors: |
Goodglick, Lee (Los Angeles, CA, US); Pietras, Richard J. (Sherman Oaks, CA, US); Mah, Vei (Davis, CA, US); Seligson, David B. (Los Angeles, CA, US); Chia, David S. (Santa Monica, CA, US); Marquez-Garban, Diana C. (Los Angeles, CA, US); Fishbein, Michael C. (Encino, CA, US) |
| Assignees: |
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA (Oakland, CA, US) |
| Claim: |
1. A method of examining a human non-small cell lung carcinoma obtained from a patient comprising the steps of observing the level of aromatase (SEQ ID NO: 2) polypeptide expressed in the non-small cell lung carcinoma, wherein the patient is female and is at least 65 years old. |
| Claim: |
2. The method of claim 1, further comprising the step of using the observed level of aromatase (SEQ ID NO: 2) polypeptide expressed in the non-small cell lung carcinoma to determine a prognosis for the patient. |
| Claim: |
3. The method of claim 2, wherein the prognosis comprises an estimate of the probability of the patient surviving for at least 1, 2, 3, 4 or 5 years from the time of the examination. |
| Claim: |
4. The method of claim 1, further comprising the step of using the observed level of aromatase (SEQ ID NO: 2) polypeptide expressed by the non-small cell lung carcinoma to evaluate a course of therapy for the patient. |
| Claim: |
5. The method of claim 4, wherein a course of therapy for the patient includes administering one or more aromatase inhibitors to the patient. |
| Claim: |
6. The method of claim 1, further comprising the step of determining if the patient has a lifetime history of smoking more than 100 cigarettes. |
| Claim: |
7. The method of claim 1, further comprising determining if the non-small cell lung carcinoma is a stage I, stage II, stage III or stage IV non-small cell lung carcinoma. |
| Claim: |
8. The method of claim 1, wherein the level of aromatase polypeptide expressed by the non-small cell lung carcinoma is observed using an assay of aromatase polypeptide enzymatic activity. |
| Claim: |
9. The method of claim 1, wherein the level of aromatase polypeptide expressed by the non-small cell lung carcinoma is observed using an antibody that binds aromatase polypeptide. |
| Claim: |
10. The method of claim 9, wherein: the antibody is used in an immunohistochemical assay of cytoplasmic aromatase staining intensity; the assay comprises a numerical scale of staining intensity values including a mean or median staining intensity value; a staining intensity value above the mean or median staining intensity value characterizes the cell as having a high level of aromatase expression; and a staining intensity value below the mean or median staining intensity value characterizes the cell as having a low level of aromatase expression. |
| Claim: |
11. The method of claim 10, wherein: the antibody is used in an immunohistochemical assay of cytoplasmic aromatase staining intensity using a value scale of 0-3; a staining intensity value of 0 corresponds to an amount of aromatase staining that is below the level of detection; a staining intensity value of 1 corresponds to a weak amount of aromatase staining; a staining intensity value of 2 corresponds to a moderate amount of aromatase staining; and a staining intensity value of 4 corresponds to a strong amount of aromatase staining; a staining intensity value above 1.5 characterizes the cell as having a high level of aromatase expression; and a staining intensity value below 1.5 characterizes the cell as having a low level of aromatase expression. |
| Claim: |
12. The method of claim 10, wherein a staining intensity value is quantified using image analysis software. |
| Claim: |
13. The method of claim 10, wherein the numerical scale of staining intensity values is derived from a plurality of stained cells having a plurality of levels of aromatase expression. |
| Claim: |
14. The method of claim 10, wherein a low level of aromatase expression identifies the patient as having a greater probability of surviving for at least 1, 2, 3, 4 or 5 years from the time of the examination than does a patient identified as having a high level of aromatase expression. |
| Claim: |
15. The method of claim 10, wherein a high level of aromatase expression identifies the patient as a candidate for treatment with an aromatase inhibitor. |
| Claim: |
16. The method of claim 1, wherein the level of aromatase polypeptide expressed in the non-small cell lung carcinoma is observed indirectly by: using a polymerase chain reaction to observe the level of aromatase mRNA in the cell that encode the aromatase polypeptide; and correlating the level of aromatase mRNA observed in the cell with the level of aromatase polypeptide expressed in the cell. |
| Claim: |
17. The method of claim 1, wherein the level of aromatase polypeptide expressed by the non-small cell lung carcinoma is observed using a high-density tissue microarray. |
| Claim: |
18. A method of obtaining information useful for determining a prognosis or therapy for a female patient having or suspected of having a human non-small cell lung carcinoma, the method comprising: observing a level of aromatase (SEQ ID NO: 2) polypeptide expressed in a tissue sample obtained from the patient that includes or is suspected of including the human non-small cell lung carcinoma cells; and correlating the level of aromatase polypeptide observed in the cells with a prognosis or therapy for non-small cell lung carcinoma that is associated with the observed level of aromatase (SEQ ID NO: 2) polypeptide expressed by the cells. |
| Claim: |
19. The method of claim 18, wherein the level of aromatase polypeptide expressed in the tissue sample is determined using an immunohistochemical staining technique; and the method further comprises determining the percentage of cells in the tissue sample that are stained in the immunohistochemical staining technique. |
| Claim: |
20. The method of claim 18, wherein: the level of aromatase polypeptide expressed in the tissue sample is determined using an immunohistochemical staining technique; the method is preformed on a plurality of patients; and the plurality of patients are stratified into those having a staining intensity in the immunohistochemical staining technique that is either above or below a mean or median staining intensity value on a numerical scale of staining intensity values derived from a plurality of stained cells having a plurality of levels of aromatase expression. |
| Claim: |
21. The method of claim 20, wherein the stratification is used to: predict the probability of the patient surviving for at least 1, 2, 3, 4 or 5 years from the time of the examination; or identify patients likely to respond to a therapeutic regimen comprising a aromatase inhibitor. |
| Claim: |
22. The method of claim 18, wherein the level of aromatase polypeptide expressed in the non-small cell lung carcinoma is observed by: observing the level of aromatase mRNA in the cell that encode the aromatase polypeptide; and correlating the level of aromatase mRNA observed in the cell with the level of aromatase polypeptide expressed in the cell. |
| Claim: |
23. The method of claim 22, wherein the aromatase mRNA is observed in the cell using a polynucleotide that hybridizes to the aromatase mRNA. |
| Claim: |
24. The method of claim 18, further comprising determining if a cell in the tissue sample is a stage I/II non-small cell lung carcinoma. |
| Claim: |
25. The method of claim 18, further comprising obtaining information useful for determining a prognosis or therapy for a female patient by: determining if the patient has a lifetime history of smoking more than 100 cigarettes; or determining the age of the patient. |
| Current U.S. Class: |
506/9 |
| Current International Class: |
40; 12; 01; 12 |
| رقم الانضمام: |
edspap.20100331203 |
| قاعدة البيانات: |
USPTO Patent Applications |
