Methods for diagnosis and prognosis of epithelial tumors
A biomarker is disclosed that can distinguish aggressive epithelial tumors in a tissue biopsy from, for example, normal, hyperplastic, and benign neoplastic tumors. The biomarker can also identify epithelial tumors that have become resistant to hormone therapy. Therefore, methods are disclosed for providing diagnosis and prognosis of a subject having, or suspected of having, an epithelial tumor, such as a prostate tumor.
1. A method for providing a prognosis of a subject with prostate cancer and treating a subject with a poor prognosis, comprising assaying a biopsy sample comprising basal cells and optimally comprising luminal cells from the subject for the level of FGD1-related F-actin binding protein (Frabin/FGD4) protein, FGD4 gene expression, or a combination thereof, and comparing the level to control values, wherein an elevated level of Frabin or FGD4 in the luminal cells and a concomitant absence of Frabin or FGD4 in basal cells is an indication of a poor prognosis; and further treating said subject with an elevated level of Frabin or FGD4 by administering to the subject a chemotherapeutic.
2. The method of claim 1 , wherein an elevated level of Frabin or FGD4 in the sample is an indication of androgen independent prostate cancer.
3. The method of claim 1 , further comprising androgen ablation if an evaluated level of Frabin or FGD4 in the cancer is detected.
4. The method of claim 1 , wherein the chemotherapeutic is selected from the group consisting of docetaxel (Taxotere®), paclitaxel (Taxol®), mitoxantrone (Novantrone®), carboplatin (Paraplatin®), and vinorelbine (Navelbine®).
5. The method of any one of claims 3 or 4 , further comprising administering to the subject an angiogenesis inhibitor if an elevated level of Frabin or FGD4 in the sample is detected.
6. The method of claim 5 , wherein the angiogenesis inhibitor comprises bevacizumab (Avastin®).
7. A method for providing a prognosis of a subject with prostate cancer who is receiving primary hormonal therapy and treating a subject who has been given a poor prognosis accordingly, comprising assaying a biopsy sample comprising basal cells and optimally comprising luminal cells from the subject for the level of FGD1-related F-actin binding protein (Frabin/FGD4) protein, FGD4 gene expression, or a combination thereof, and comparing the level to control values, wherein an elevated level of Frabin or FGD4 in the luminal cells and a concomitant absence of Frabin or FGD4 in basal cells is an indication of a poor prognosis; and terminating primary hormonal therapy when the subject has an elevated level of Frabin or FGD4 in the sample.
8. The method of claim 7 , wherein the primary hormonal therapy is an antiandrogen, such as Bicalutamide (Casodex®), Flutamide (Drogenil®), or Enzalutamide (Xtandi®).