Class characterization of circulating cancer cells isolated from body fluids and methods of use
The present invention relates to the identification and characterization of classes and subclasses of circulating cancer cells, including microtumors from body fluid samples using molecular, cytological, and morphological analyses, and methods for staging patients and measuring the efficacy of medical treatments.
1. A method of classifying epithelial cancer cells in a sample of blood from a patient with cancer or a patient suspected of having cancer, said method comprising: isolating circulating epithelial cancer cells from said sample, and classifying said isolated cancer cells as terminal cells or proliferative cells by cytological and morphological analyses using fluorescence microscopy.
2. The method of claim 1 , wherein at least one cancer cell is a terminal cell that is a fragile, large cancer cell compared to a white blood cell from the patient, and with a high nucleus to cytoplasm ratio when compared to a white blood cell from the patient.
3. The method of claim 2 , wherein said terminal cell is about 20 micrometers to about 50 micrometers in diameter.
4. The method of claim 1 , wherein at least one cancer cell is a terminal cell that is a fragile, large cancer cell compared to a white blood cell from the patient, and is without a nucleus.
5. The method of claim 4 , wherein said terminal cell is about 20 micrometers to about 40 micrometers in diameter.
6. The method of claim 1 , wherein at least one cancer cell is a terminal cell with a nucleus.
7. The method of claim 6 , wherein said terminal cell is a late-stage dying cell and is breaking into pieces.
8. The method of claim 1 , wherein at least one cancer cell is a proliferative cell.
9. The method of claim 8 , wherein said cancer cell is about 25-35 micrometers in diameter.
10. The method of claim 8 , wherein said cancer cell is a proliferative cell that is a dividing cell.
11. The method of claim 1 , wherein three to 100 of said isolated cancer cells are in the form of a microtumor.
12. A method of determining the presence or absence of epithelial cancer cells capable of causing metastatic cancer, said method comprising:
(a) isolating circulating epithelial cancer cells in a sample of blood from a patient with cancer or a patient suspected of having cancer; and
(b) classifying said isolated cancer cells as terminal cells or proliferative cells by cytological and morphological analyses using fluorescence microscopy, thereby determining the presence or absence of cancer cells capable of causing metastatic cancer.
13. A method of determining the efficacy of a medical procedure for treatment of cancer in a patient, said method comprising:
(a) conducting a first isolation of circulating epithelial cancer cells in a sample of blood from the patient;
(b) classifying said isolated cancer cells as terminal cells or proliferative cells by cytological and morphological analyses using fluorescence microscopy;
(c) conducting a second isolation of circulating epithelial cancer cells in a sample of blood from the patient;
(d) repeating (b) on said second isolated cancer cells; and
(e) comparing the number of said first isolated cancer cells to the number of said second isolated cancer cells, or comparing the classes of said first isolated cancer cells to the classes of said second isolated cancer cells, wherein the first isolation is conducted before the administration of the medical procedure and the second isolation is conducted after the administration of the medical procedure, thereby determining the efficacy of said medical procedure.
14. The method of claim 13 , wherein the presence of more terminal cells in the second isolation than in the first isolation is indicative of a positive response to the medical procedure.
15. The method of claim 13 , wherein the presence of more proliferative cells in the second isolation than in the first isolation is indicative of a negative response to the medical procedure.
16. The method of claim 13 , wherein an increase or no change in the level of circulating cancer cells during or after terminating the medical procedure is indicative of a negative response to the medical procedure.
17. The method of claim 13 , wherein said medical procedure is selected from the group consisting of surgery, radiation, hormone therapy, gene therapy, and therapeutic agent(s) administration, and a combination thereof.
18. The method of any one of claims 1 , 12 and 13 , wherein said cancer cells are breast cancer cells.
19. The method of any one of claims 1 , 12 and 13 , wherein said cancer cells are prostate cancer cells.